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A rapid, microenzymatic method was used to measure cerebrospinalfluid lactate levels in 205 children with suspected bacterial meningitis. Fifty children with normal CSF containing fewer than 0.005 X 10(9)/l WBC, no segmented neutrophils, glucose 3.4 +/- 0.8 mmol/l (61.2 +/- 14.4 mg/100 ml), and a protein of less than 0.30 g/l had CSF lactate levels below 2.0 mmol/l (18 mg/100 ml) (mean and standard deviation 1.3 +/- 0.3 mmol/l (11.8 +/- 2.7 mg/100 ml)). In 31 cases of proved viral meningitis as with 58 cases of clinically diagnosed viral meningitis, levels were below 3.8 mmol/l (34.5 mg/100 ml), being 2.3 +/- 0.6 mmol/l (20.9 +/- 5.4 mg/100 ml), and 2.1 +/- 0.7 mmol/l (19.1 +/- 6.4 mg/100 ml) respectively. Sixty-six cases of bacterial meningitis had CSF lactate levels ranging from 3.9 mmol/l (35.4 mg/100 ml) to greater than 10.0 mmol/l (90.0 mg/100 ml). Longitudinal studies in 7 children with bacterial meningitis showed that cerebrospinalfluid lactate levels differentiated bacterial from viral meningitis up to 4 days after starting treatment with antibiotics. Use of CSF lactate measurement for monitoring the efficacy of treatment is illustrated in a case of bacterial meningitis due to Pseudomonas aeruginosa. The origin of the cerebrospinalfluid lactate acidosis and the role of lactate in the pathophysiological cycle leading to intensification of brain tissue hypoxia and cellular damage is discussed with respect to the short-term prognosis and the long-term neurological sequelae.
Background and Purpose: Hepatocyte growth factor (HGF) is a multifunctional cytokine that has been found to be elevated in tuberculous and bacterial meningitis, but no evaluation has been undertaken of its usefulness in identifying various forms of aseptic meningitis. Methods: In a retrospective study, the levels of HGF in the cerebrospinalfluid of 65 patients were measured prior to treatment.
Objective: Cerebrospinalfluid parameters are of great importance in diagnosing meningitis, but normal values for preterm neonates are based on small, single-center studies. We sought to determine current values for preterm neonate cerebrospinalfluid parameters and assess the association of cerebrospinalfluid parameters with culture proven meningitis. Study Design: Cohort study of the first lumbar puncture from 4,632 neonates <34 weeks gestation performed in the years 1997-2004 at 150 neonatal intensive care units managed by the Pediatrix Medical Group. Results: We identified 95 cases of meningitis from the 4,632 lumbar punctures. The area under the receiver operating characteristic curves for white blood cell count, glucose, and protein were 0.80, 0.63, and 0.72 respectively for prediction of culture proven meningitis. Conclusion: Cerebrospinalfluid parameters used to diagnose meningitis in the absence of dependable cerebrospinalfluid cultures are unreliable. Caution should be employed when interpreting cerebrospinalfluid parameters in the premature neonate.
Smith, P. Brian; Garges, Harmony P.; Cotten, C. Michael; Walsh, Thomas J.; Clark, Reese H.; Benjamin, Daniel K.
Objective?To determine the risk factors for and the clinical course of postoperative meningitis following lateral skull base surgery and to determine its relationship to cerebrospinalfluid (CSF) fistula. Patients?Patients undergoing lateral skull base surgery between July 1999 and February 2010 at an academic tertiary referral center. All subjects had culture-proven meningitis or suspected bacterial meningitis in the postoperative period. Medical records were compared with the lateral skull base patients who did not develop meningitis. Results?Of 508 procedures, 16 patients developed meningitis (3.1%). The most common diagnosis was acoustic neuroma in 81.3%; 68.8% of patients had a CSF leak prior to onset of meningitis, and 50% received a lumbar drain. The median time from surgery to the onset of meningitis was 12 days with a range of 2 to 880 days. The relative risk of developing meningitis in the setting of postoperative CSF fistula is 10.2 (p?0.0001). No meningitis-associated mortality was observed. Conclusions?Postoperative meningitis occurred in a small number of patients undergoing lateral skull base surgery. A postoperative CSF fistula leads to an increased risk of meningitis by a factor of 10.2.
Allen, Kyle P.; Isaacson, Brandon; Kutz, J. Walter; Purcell, Patricia L.; Roland, Peter S.
Objectives: cerebrospinalfluid (CSF) levels of interleukin (IL)-1 ? and tumor necrosis factor (TNF) a were measured to assess the effect and application of dexamethasone (Dex) therapy for bacterial meningitis.Methods: associations between clinical findings and CSF parameters were first investigated, and prognosis was compared between 25 patients with Dex and 12 without Dex therapy.Results: patients with the presence of disturbed
BACKGROUND: A low cerebrospinalfluid (CSF) white-blood cell count (WBC) has been identified as an independent risk factor for adverse outcome in adults with bacterial meningitis. Whereas a low CSF WBC indicates the presence of sepsis with early meningitis in patients with meningococcal infections, the relation between CSF WBC and outcome in patients with pneumococcal meningitis is not understood. METHODS:
Martijn Weisfelt; Diederik van de Beek; Lodewijk Spanjaard; Johannes B Reitsma; Jan de Gans
Cerebrospinalfluid (CSF) anti-mycobacterial antigen 60 (A60) IgM, IgG and IgA in patients affected by meningitis of different etiologies were assayed as a rapid diagnostic test in cases of tuberculous meningitis. A commercial EIA was used to test 127 CSF samples classified as follows: tuberculous meningitis (n=27 CSF samples from 16 patients, 6 of them with AIDS), pyogenic meningitis (n=13),
L. F. López-Cortés; M. C. Nogales-Pérez; J. Gómez-Mateos; D. Jiménez-Hernández; E. Jiménez-Mejias; J. Pachón-Diaz
In exceptional cases, patients with aseptic meningitis eventually develop aseptic meningoencephalitis. To find a candidate marker for the development of aseptic meningoencephalitis in adult patients diagnosed with aseptic meningitis, we compared 12 different cytokines/chemokines in cerebrospinalfluid (CSF) from 5 patients with aseptic meningoencephalitis, 8 patients with aseptic meningitis, and 8 patients with control disease. Only the CXCL13 concentration was significantly elevated in the CSF of the group with aseptic meningoencephalitis compared with the group with aseptic meningitis. Thus, CSF CXCL13 may be a useful marker for predicting the prognosis of aseptic meningitis. PMID:24907903
CXCL5 (epithelial-cell-derived neutrophil-activating protein (ENA-)78) is a CXC-chemokine that specifically acts on neutrophils. To obtain insight into the extent of local presence and action of CXCL5 during bacterial meningitis, we measured its concentrations in cerebrospinalfluid (CSF) of patients with culture-proven bacterial meningitis (n=14), aseptic meningitis (n=6), and controls (n=32) and compared these results with levels of other CXC-chemokines, CXCL8-
Petra J. G. Zwijnenburg; Henrica M. A. de Bie; John J. Roord; Tom van der Poll; A. Marceline van Furth
Forty-one patients suffering from group A meningococcal meningitis in an area within the epidemic meningococcal belt of tropical West Africa were studied. The serum of only two of these patients contained fibrin degradation products (FDPs). The cerebrospinalfluid of 21 of these cases was also examined for FDPs, which were present in 13. Their presence in the cerebrospinalfluid was associated with a poor prognosis. PMID:4212012
Brueton, M J; Tugwell, P; Whittle, H C; Greenwood, B M
Forty-one patients suffering from group A meningococcal meningitis in an area within the epidemic meningococcal belt of tropical West Africa were studied. The serum of only two of these patients contained fibrin degradation products (FDPs). The cerebrospinalfluid of 21 of these cases was also examined for FDPs, which were present in 13. Their presence in the cerebrospinalfluid was associated with a poor prognosis.
Brueton, M. J.; Tugwell, P.; Whittle, H. C.; Greenwood, B. M.
Background: Some important clinical differences exist between human immunodeficiency virus (HIV)-seropositive and HIV-seronegative patients. Alterations in the cerebrospinalfluid (CSF) cytokines and matrix metalloproteinase have been noted in tuberculous meningitis. In HIV-infected patients, the immunopathogenesis is expected to be different. Materials and Methods: In this study, 64 patients of tuberculous meningitis (28 HIV seropositive and 36 seronegative) were included. The patients were followed up for six months. Cerebrospinalfluid (CSF) samples of tuberculous meningitis patients and 20 controls were subjected to tissue necrosis factor (TNF)-?, interleukin (IL)-1?, interferon (IFN)-?, IL-10, matrix metalloproteinase (MMP)-2, and MMP-9 estimations. The levels were correlated with the patients’ baseline clinical characteristics, CSF parameters, neuroimaging findings, and the outcome. The outcome was assessed and modified with the Barthel index. Results: The CSF cytokines and MMP levels were significantly elevated in tuberculous meningitis when compared with the controls. There was no significant difference seen between HIV seropositive and seronegative tuberculous meningitis, except for the IL-1? level, which was significantly lower in the HIV-infected patients. The cytokine and MMP levels did not correlate with the baseline clinical characteristics, disease severity, cerebrospinalfluid characteristics, neuroimaging findings, and outcome. Conclusion: In conclusion, HIV infection did not affect a majority of the CSF cytokines and MMP levels in tuberculous meningitis except for IL-1? level. None of the estimated inflammatory parameters correlated with the outcome.
Background Early differential diagnosis between acute bacterial and viral meningitis is problematic. We aimed to investigate whether the detection of lipocalin 2, a protein of the acute innate immunity response, may be used as a marker for acute bacterial meningitis. Methods Transgenic mice expressing the human transferrin were infected by intraperitoneal route and were imaged. Cerebrospinalfluid (CSF) was sampled up to 48hours post- infection to measure lipocalin 2. We also tested a collection of 90 and 44 human CSF with confirmed acute bacterial or acute viral meningitis respectively. Results Lipocalin 2 was detected after 5 h in CSF during experimental infection in mice. Lipocalin 2 levels were significantly higher (p?0.0001) in patients with confirmed acute bacterial meningitis (mean 125 pg/mL, range 106–145 pg/mL) than in patients with acute viral meningitis (mean 2 pg/mL, range 0–6 pg/mL) with a sensitivity of 81%, a specificity of 93%, a positive predictive value of 96% and a negative predictive value of 71% in diagnosing acute bacterial meningitis. Conclusions Increased levels of lipocalin 2 in cerebrospinalfluid may discriminate between acute bacterial and viral meningitis in patients with clinical syndrome of meningitis.
Background: The prevalence of tuberculous meningitis (TBM) is very high in developing areas of the world. Inflammation and cytokine patterns produced by T lymphocytes play an important role in susceptibility to infections. The inflammatory response and production of cytokines in the cerebrospinalfluid (CSF) of patients with TBM are well documented. Conversely, little is known about the role of pro-
Rajpal S. Kashyap; Poonam S. Deshpande; Sonali R. Ramteke; Milind S. Panchbhai; Hemant J. Purohit; Girdhar M. Taori; Hatim F. Daginawala
Human enteroviruses are the most common cause of viral meningitis. Viral-bacterial interaction may affect the clinical course and outcome of bacterial meningitis. In Africa, viruses might be responsible for 14-25% of all meningitis cases. However, only few studies from Africa have reported detection of viruses in the cerebrospinalfluid (CSF) or mixed viral-bacterial infections of the central nervous system (CNS). The aim of the present study was to investigate the presence of picornaviruses in the CSF of children suffering from meningitis in Luanda, Angola. The study included 142 consecutive children enrolled in a prospective study of bacterial meningitis in Luanda between 2005 and 2006, from whom a CSF sample was available. CSF samples were obtained at hospital admission, stored in a deep-freeze, and transported to Finland for testing by real-time PCR for picornaviruses. Enteroviruses were detected in 4 (3%) of 142 children with presumed bacterial meningitis. A 5-month-old girl with rhinovirus and Haemophilus influenzae meningitis recovered uneventfully. An 8-year-old girl with human enterovirus and pneumococcal meningitis developed no sequelae. A 2-month-old girl with human enterovirus and malaria recovered quickly. A 7-month-old girl with human enterovirus was treated for presumed tuberculous meningitis and survived with severe sequelae. Mixed infections of the CNS with picornaviruses and bacteria are rare. Detection of an enterovirus does not affect the clinical picture and outcome of bacterial meningitis. PMID:22585725
The pharmacokinetics of fluconazole, a new oral azole, were evaluated in cerebrospinalfluid and sera of eight patients with coccidioidal meningitis. At a dose of 50 mg/day, peak concentrations of 2.5 to 3.5 and 2.0 to 2.3 micrograms/ml occurred at 2 to 6 and 4 to 8 h in serum and cerebrospinalfluid, respectively. At 100 mg/day, peak concentrations of 4.5 to 8.0 and 3.4 to 6.2 micrograms/ml occurred at 2 to 4 and 4 to 12 h, respectively. The mean ratios of the concentration in cerebrospinalfluid to that in serum were 73.8% at 50 mg/day and 88.7% at 100 mg/day. Results suggested that there was a prolonged half-life in both cerebrospinalfluid and serum and that it was slightly longer in the former. Minimal toxicity was noted in 34 patient months of therapy (12 months on 50 mg daily; 22 months on 100 mg daily). After a mean of 4.5 months of therapy, five patients responded to therapy and three were unevaluable. The penetration of fluconazole into cerebrospinalfluid was substantial, toxicity was minimal, and early clinical experience was encouraging. Fluconazole holds promise as the sole or adjunctive therapy for fungal meningitis.
Tucker, R M; Williams, P L; Arathoon, E G; Levine, B E; Hartstein, A I; Hanson, L H; Stevens, D A
The pharmacokinetics of fluconazole, a new oral azole, were evaluated in cerebrospinalfluid and sera of eight patients with coccidioidal meningitis. At a dose of 50 mg/day, peak concentrations of 2.5 to 3.5 and 2.0 to 2.3 micrograms/ml occurred at 2 to 6 and 4 to 8 h in serum and cerebrospinalfluid, respectively. At 100 mg/day, peak concentrations of 4.5 to 8.0 and 3.4 to 6.2 micrograms/ml occurred at 2 to 4 and 4 to 12 h, respectively. The mean ratios of the concentration in cerebrospinalfluid to that in serum were 73.8% at 50 mg/day and 88.7% at 100 mg/day. Results suggested that there was a prolonged half-life in both cerebrospinalfluid and serum and that it was slightly longer in the former. Minimal toxicity was noted in 34 patient months of therapy (12 months on 50 mg daily; 22 months on 100 mg daily). After a mean of 4.5 months of therapy, five patients responded to therapy and three were unevaluable. The penetration of fluconazole into cerebrospinalfluid was substantial, toxicity was minimal, and early clinical experience was encouraging. Fluconazole holds promise as the sole or adjunctive therapy for fungal meningitis. PMID:2835002
Tucker, R M; Williams, P L; Arathoon, E G; Levine, B E; Hartstein, A I; Hanson, L H; Stevens, D A
Background Cerebrospinalfluid (CSF) lactate is a potential biomarker for bacterial meningitis in children. To this end, we performed a single-center retrospective cohort study of children from Sao Paulo, Brazil, with CSF pleocytosis to evaluate the ability of CSF lactate to distinguish between children with bacterial and aseptic meningitis. We determined the optimum cutoff point for CSF lactate using receiver-operator curve (ROC) analysis. Findings We identified 451 children of whom 40 (9%) had bacterial meningitis. Children with bacterial meningitis had a higher median CSF lactate level [9.6 mmol/l, interquartile range (IQR) 3.2-38.5 mmol/l bacterial meningitis vs. 2.0 mmol/l, IQR 1.2-2.8 mmol/l aseptic meningitis]. A CSF lactate cutoff point of 3.0 mmol/l had a sensitivity of 95% [95% confidence interval (CI) 83-99%), specificity of 94% (95% CI 90-96%) and negative predictive value of 99.3% (95% CI 97.7-99.9%) for bacterial meningitis. Conclusions In combination with a validated meningitis clinical prediction rule, the CSF lactate level can be used to distinguish between bacterial and aseptic meningitis in children with CSF pleocytosis.
Vascular endothelial growth factor (VEGF) is a potent vascular permeability factor and a mediator of brain edema. To assess the role of VEGF during bacterial meningitis, VEGF was measured in cerebrospinalfluid (CSF) and blood of 37 patients with bacterial meningitis and 51 control patients, including 16 patients with viral meningitis. Circulating VEGF levels were similar in bacterial meningitis patients and control patients. VEGF(CSF) was detected in 11 (30%) of 37 of bacterial meningitis patients (range, <25-633 pg/mL) but in none of the control patients. The median VEGF index was 6.2 (range, 0.6-42), indicating intrathecal production. Median CSF cell counts, protein levels, and CSF: serum albumin ratios were higher for patients with detectable VEGF(CSF), although the difference was not statistically significant. VEGF immunoreactivity in autopsy brain specimens was found in the inflammatory infiltrate of patients with bacterial meningitis. These results indicate that inflammatory cells secrete VEGF during bacterial meningitis and that VEGF may contribute to blood-brain barrier disruption. PMID:11106541
van der Flier, M; Stockhammer, G; Vonk, G J; Nikkels, P G; van Diemen-Steenvoorde, R A; van der Vlist, G J; Rupert, S W; Schmutzhard, E; Gunsilius, E; Gastl, G; Hoepelman, A I; Kimpen, J L; Geelen, S P
Rifampin was administered orally in one dose of 25 mg per kg of body weight to 6 patients with tuberculous meningitis who had received no previous antituberculous chemotherapy and to 7 control subjects. There was no sigificant difference in rifampin absor...
J. E. Sippel I. A. Mikhail N. I. Girgis H. H. Youssef
Measurement of cerebrospinalfluid lactic acid by an enzymatic test has been evaluated in 164 patients. The upper limit of normal CSF lactate was 300 mg/l. The CSF lactate level is useful for differential diagnosis between partially treated pyogenic meningitis and tuberculous meningitis. The increase of CSF lactate is not specific for meningitis and must be interpreted taking into account the clinical situation. PMID:3892450
el Mdaghri, N; Benbachir, M; Tazi-Lakhsassi, L; Himmich, H
Tuberculous meningitis (TBM) is a serious complication of tuberculosis that affects the central nervous system. Present methods to diagnose TBM are not suitable for early diagnosis. Molecular markers and sensitive methods to identify them in the early stage of infection of TBM are critically needed for efficient management. We have done the proteomic analysis of TBM cerebrospinalfluid (n=20) with 2-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry. We identified 11 human proteins and 8 mycobacterial proteins with changed expression levels in comparison to controls. Arachidonate 5-lipoxygenase and glial fibrillary acidic protein, two of the identified proteins, were validated with western blot technique on a larger set of disease and control samples (n=40). These two proteins were also analyzed in fungal meningitis samples. We suggest that arachidonate 5-lipoxygenase can be considered for validation as a potential marker for diagnosis of TBM. PMID:21723968
The organotrophic functions of the hepatocyte growth factor (HGF) have been the subject of several studies. In the more recent studies, this function has been reported in the brain. In the present study, we have measured the levels of HGF in cerebrospinalfluid (CSF) and sera from 78 patients divided into 6 different groups according to central nervous system (CNS) infection and control. Quantitative measurements of HGF in the CSF and serum were performed by an enzyme-linked immunosorbent assay. Elevated values of CSF HGF were found in the patients with acute bacterial/probable bacterial meningitis (P<.001), compared with nonbacterial CNS infections and facial palsy, as well as with a control group without signs of CNS involvement. The values of CSF HGF were not correlated to blood-brain-barrier disruption in the groups. These observations might indicate an intrathecal production of HGF in acute bacterial/probable bacterial meningitis. PMID:10837201
Nayeri, F; Nilsson, I; Hagberg, L; Brudin, L; Roberg, M; Söderström, C; Forsberg, P
Enterovirus infections were investigated with special emphasis on performing rapid molecular identification of enterovirus serotypes responsible for aseptic meningitis directly in cerebrospinalfluid (CSF). Enterovirus genotyping was carried out directly with specimens tested for the diagnostic procedure, using two seminested PCR assays designed to amplify the complete and partial gene sequences encoding the VP1 and VP4/VP2 capsid proteins, respectively. The method was used for identifying the enterovirus serotypes involved in meningitis in 45 patients admitted in 2005. Enterovirus genotyping was achieved in 98% of the patients studied, and we obtained evidence of 10 of the most frequent serotypes identified earlier by genotyping of virus isolates. The method was applied for the prospective investigation of 54 patients with meningitis admitted consecutively in 2006. The enterovirus serotypes involved were identified with the cerebrospinalfluid (CSF) of 52 patients (96%) and comprised 13 serotypes within the human enterovirus B species and 1 within the human enterovirus A species. The three most common serotypes were echovirus 13 (E13; 24%), E6 (23%), and coxsackievirus B5 (11.5%), a pattern different from that observed in 2005. Genotyping of virus isolates was also performed in 35 patients in 2006 (meningitis, n = 31; other diseases, n = 4). By comparison, direct genotyping in CSF yielded a more complete pattern of enterovirus serotypes, thereby allowing the detection of rare serotypes: three less common serotypes (CB2, E21, and E27) were not detected by indirect genotyping alone. The study shows the feasibility of prospective enterovirus genotyping within 1 week in a laboratory setting.
Introduction Outcomes following bacterial meningitis are significantly improved by adjunctive treatment with corticosteroids. However, little is known about the levels and significance of intrathecal endogenous cortisol. The aim of this study was to assess cortisol as a biological and diagnostic marker in patients with bacterial meningitis. Methods Forty-seven consecutive patients with bacterial meningitis and no prior treatment were evaluated. For comparison, a group of 37 patients with aseptic meningitis and a group of 13 healthy control individuals were included. Results The mean age of the bacterial meningitis patients was 42 years, and the mean Glasgow Coma Scale, Acute Physiology and Chronic Health Evaluation II, and Sequential Organ Failure Assessment scores on admission were 12, 13 and 4, respectively. Altogether, 40 patients (85%) were admitted to the intensive care unit, with a median (interquartile range) length of stay of 8 (4 to 15) days. A bacterial etiology was confirmed in 35 patients (74%). The median (interquartile range) cortisol concentration in cerebrospinalfluid (CSF) was 133 (59 to 278) nmol/l. CSF cortisol concentrations were positively correlated with serum cortisol levels (r = 0.587, P < 0.001). Furthermore, CSF cortisol levels correlated with Acute Physiology and Chronic Health Evaluation II score (r = 0.763, P < 0.001), Sequential Organ Failure Assessment score (r = 0.650, P < 0.001), Glasgow Coma Scale score (r = -0.547, P < 0.001) and CSF lactate levels (r = 0.734, P < 0.001). CSF cortisol was only weakly associated with intrathecal levels of IL-6 (r = 0.331, P = 0.02) and IL-8 (r = 0.296, P < 0.05). CSF cortisol levels in bacterial and aseptic meningitis significantly differed (P < 0.001). The CSF cortisol concentration of 46.1 nmol/l was found to be the optimal cutoff value for diagnosis of bacterial meningitis. Conclusion CSF cortisol levels in patients with bacterial meningitis are highly elevated and correlate with disease severity. Moreover, our findings also suggest that intrathecal cortisol may serve as a valuable marker in discriminating between bacterial and aseptic meningitis.
Thirty-seven matched cerebrospinalfluid (CSF) and plasma samples from 34 human immunodeficiency virus type 1 (HIV-1)-infected patients with suspected meningitis were analyzed for levels of HIV-1 RNA and markers of inflammation. Patients with tuberculous (n = 9) or cryptococcal (n = 6) meningitis had the highest CSF virus loads, which in many cases exceeded the levels in plasma, compared with patients with meningococcal meningitis (n = 3), aseptic meningitis (n = 8), tuberculoma (n = 2), or AIDS dementia complex (n = 4) or with normal lumbar punctures (n = 3). CSF virus load correlated significantly with the number of infiltrating lymphocytes (r = .60, P < .001) but not with plasma virus load, the levels of beta2-microglobulin in the CSF, or the integrity of the blood-brain barrier. These data suggest significant intrathecal HIV-1 replication in patients with lymphocytic meningeal infections such as tuberculous and cryptococcal meningitis. PMID:9466541
Morris, L; Silber, E; Sonnenberg, P; Eintracht, S; Nyoka, S; Lyons, S F; Saffer, D; Koornhof, H; Martin, D J
It has been suggested that genetic variants in mannose binding lectin (MBL2) influence susceptibility and outcome of invasive pneumococcal disease. We assessed the influence of genetic variation in MBL2 on susceptibility, outcome and causative serotype of pneumococcal meningitis in a prospective nationwide cohort study including 299 white patients and 216 controls. We assessed functionality of the genetic polymorphisms by measuring levels of MBL, C3a, iC3b, C5a and sC5b-9 in cerebrospinalfluid. We also performed a meta-analysis of studies on MBL2 polymorphisms and susceptibility to invasive pneumococcal disease. The risk of contracting pneumococcal meningitis was substantially increased for white individuals homozygous with the defective MBL2 0/0 genotype (odds ratio [OR] 8.21, 95% confidence interval [CI] 1.05–64.1; p?=?0.017). CSF MBL levels were significantly lower in patients with the A/0 and 0/0 genotype compared to homozygotes for the wild-type alleles (A/A; p<0.001). CSF MBL levels were positively correlated with C3a and iC3b levels, indicating complement activation by the lectin pathway. The effect of MBL2 genetic variants on susceptibility remained robust in a meta-analysis including 5 studies with 287 patients (OR 2.33, 99% CI 1.39–3.90). We conclude that MBL2 polymorphisms influence CSF MBL levels and substantially increase the risk of pneumococcal meningitis.
Brouwer, Matthijs C.; Baas, Frank; van der Ende, Arie; van de Beek, Diederik
In this letter, we propose a novel method for diagnosis of tuberculous meningitis using Raman spectroscopy. The silicate Raman signature obtained from Mycobacterium tuberculosis positive cases enables specific and sensitive detection of tuberculous meningitis from acquired cerebrospinalfluid samples. The association of silicates with the tuberculosis mycobacterium is discussed. We envision that this new method will facilitate rapid diagnosis of tuberculous meningitis without application of exogenous reagents or dyes and can be aptly used as a complementary screening tool to the existing gold standard methods. PMID:22887773
The penetration of amikacin into the cerebrospinalfluid (CSF) was studied with 16 children (mean age, 1 year and 9 months; range, 4 months to 8 years) with community-acquired bacterial meningitis. Amikacin was given intravenously at a dose of 7.5 mg/kg of body weight twice daily. CSF was collected on day 1, at the expected peak concentration of amikacin in CSF. The mean (standard deviation) concentration of amikacin in CSF was 1.65 (1.6) mg/liter. Concentrations of amikacin in CSF correlated significantly with CSF glucose levels on admission. The mean concentrations of amikacin in CSF were 2.9, 1.1, and 0.20 mg/liter in patients with CSF glucose levels of < 1, 1 to 2, and > 2 mmol/liter, respectively. Thus, amikacin penetrates the blood-brain barrier substantially in children with bacterial meningitis and achieves particularly high concentrations when CSF glucose level is < 1 mmol/liter on admission.
We determined cefotaxime and desacetyl-cefotaxime concentrations in children with bacterial meningitis receiving high-dose cefotaxime (300 mg/kg of body weight/day) and concomitant dexamethasone therapy. The median peak cerebrospinalfluid cefotaxime and desacetyl-cefotaxime concentrations were 4.7 and 8.1 microg/ml, respectively. In vitro bactericidal activity (>99.9% killing in 6 h) was found in 17 (94%), 13 (72%), and 8 (44%) of 18 cerebrospinalfluid specimens against cefotaxime-susceptible, -intermediate (MIC, 1 microg/ml), and -resistant (MIC, 4 microg/ml) strains, respectively. High-dose cefotaxime, while safe, is not reliably sufficient therapy for cephalosporin-nonsusceptible pneumococcal meningitis, and combination therapy is recommended.
Background The central nervous system is considered a sanctuary site for HIV-1 replication. Variables associated with HIV cerebrospinalfluid (CSF) viral load in the context of opportunistic CNS infections are poorly understood. Our objective was to evaluate the relation between: (1) CSF HIV-1 viral load and CSF cytological and biochemical characteristics (leukocyte count, protein concentration, cryptococcal antigen titer); (2) CSF HIV-1 viral load and HIV-1 plasma viral load; and (3) CSF leukocyte count and the peripheral blood CD4+ T lymphocyte count. Methods Our approach was to use a prospective collection and analysis of pre-treatment, paired CSF and plasma samples from antiretroviral-naive HIV-positive patients with cryptococcal meningitis and assisted at the Francisco J Muñiz Hospital, Buenos Aires, Argentina (period: 2004 to 2006). We measured HIV CSF and plasma levels by polymerase chain reaction using the Cobas Amplicor HIV-1 Monitor Test version 1.5 (Roche). Data were processed with Statistix 7.0 software (linear regression analysis). Results Samples from 34 patients were analyzed. CSF leukocyte count showed statistically significant correlation with CSF HIV-1 viral load (r = 0.4, 95% CI = 0.13-0.63, p = 0.01). No correlation was found with the plasma viral load, CSF protein concentration and cryptococcal antigen titer. A positive correlation was found between peripheral blood CD4+ T lymphocyte count and the CSF leukocyte count (r = 0.44, 95% CI = 0.125-0.674, p = 0.0123). Conclusion Our study suggests that CSF leukocyte count influences CSF HIV-1 viral load in patients with meningitis caused by Cryptococcus neoformans.
The penetration of ceftriaxone into cerebrospinalfluid (CSF) was studied with 11 children (mean age: 2 years, 4 months; range: 4 months to 8 years) with meningitis, receiving dexamethasone (0.15 mg/kg of body weight intravenously four times daily) as adjunctive therapy. Ceftriaxone was given intravenously at doses of 50 mg/kg twice daily to patients < 18 months old and 100 mg/kg once daily to patients > or = 18 months old. CSF was collected after 1 day of treatment at the expected peak concentration of ceftriaxone in CSF. Concentrations of ceftriaxone in CSF ranged from 0.7 to 9.2 mg/liter, with a mean value of 4.0 (standard deviation [SD], 2.9) mg/liter. Values were significantly higher for patients with CSF glucose levels of < 1 mmol/liter on admission to the hospital than for patients with CSF glucose levels of > or = 1 mmol/liter (mean values of 7.1 [SD, 2.2] mg/liter versus 2.2 [SD, 1.1] mg/liter; P < 0.001). After 1 day of treatment, ceftriaxone concentrations in the CSF of children receiving dexamethasone are similar to the mean values reported for children not treated with dexamethasone. PMID:8067769
The penetration of ceftriaxone into cerebrospinalfluid (CSF) was studied with 11 children (mean age: 2 years, 4 months; range: 4 months to 8 years) with meningitis, receiving dexamethasone (0.15 mg/kg of body weight intravenously four times daily) as adjunctive therapy. Ceftriaxone was given intravenously at doses of 50 mg/kg twice daily to patients < 18 months old and 100 mg/kg once daily to patients > or = 18 months old. CSF was collected after 1 day of treatment at the expected peak concentration of ceftriaxone in CSF. Concentrations of ceftriaxone in CSF ranged from 0.7 to 9.2 mg/liter, with a mean value of 4.0 (standard deviation [SD], 2.9) mg/liter. Values were significantly higher for patients with CSF glucose levels of < 1 mmol/liter on admission to the hospital than for patients with CSF glucose levels of > or = 1 mmol/liter (mean values of 7.1 [SD, 2.2] mg/liter versus 2.2 [SD, 1.1] mg/liter; P < 0.001). After 1 day of treatment, ceftriaxone concentrations in the CSF of children receiving dexamethasone are similar to the mean values reported for children not treated with dexamethasone.
Cerebrospinalfluid (CSF) and serum B2-microglobulin (B2m) levels were measured prospectively in 63 patients with hematological malignancies and 14 patients with solid tumours to evaluate the correlation between elevated levels and malignant infiltration of meninges. Serial CSF B2-m levels were also measured in 18 patients who received prophylactic intrathecal cytotoxic treatment. CSF B2-m levels were significantly higher in patients with central nervous system (CNS) involvement than in those without (p less than 0.001). A CSF B2-m level greater than 1.80 mg/L was closely associated with CNS disease (specificity 96%, sensitivity 76%) and CNS infiltration was also likely when the CSF B2-m level exceeded a simultaneously drawn serum level (specificity 98%, sensitivity 46%). Intrathecal methotrexate prophylaxis resulted in a consistent and significant rise in CSF B2-m levels with an average increase of 96% during a course of intrathecal injections. These results suggest that CSF B2-m levels may not be helpful for predicting early CNS relapse in these patients. However the CSF B2-m level and the corresponding serum B2-m level is a useful adjunct to the cytological diagnosis of CNS involvement by malignancy at presentation. Its value in predicting early CNS relapse and documenting response to CNS treatment requires further clarification. PMID:2194155
Jeffery, G M; Frampton, C M; Legge, H M; Hart, D N
Mortality from adult bacterial meningitis exceeds 50% in sub-Saharan Africa. We postulated that—particularly in individuals infected with human immunodeficiency virus (HIV)—herpes simplex virus, varicella zoster virus, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) in the cerebrospinalfluid (CSF) contribute to poor outcome. CSF from 149 Malawian adults with bacterial meningitis and 39 controls were analyzed using polymerase chain reaction. EBV was detected in 79 of 149 bacterial meningitis patients. Mortality (54%) was associated with higher CSF EBV load when adjusted for HIV (P = .01). CMV was detected in 11 of 115 HIV-infected patients, 8 of whom died. The mechanisms by which EBV and CMV contribute to poor outcome require further investigation.
Benjamin, Laura A.; Cartwright, Katharine; Ajdukiewicz, Katherine M. B.; Cohen, Danielle B.; Menyere, Mavis; Galbraith, Sareen; Guiver, Malcolm; Neuhann, Florian; Solomon, Tom; Lalloo, David G.; Heyderman, Robert S.
Background. The brain's inflammatory response to the infecting pathogen determines the outcome of bacterial meningitis (BM), for example, the associated mortality and the extent of brain injury. The inflammatory cascade is initiated by the presence of bacteria in the cerebrospinalfluid (CSF) activating resident immune cells and leading to the influx of blood derived leukocytes. To elucidate the pathomechanisms behind the observed difference in outcome between different pathogens, we compared the inflammatory profile in the CSF of patients with BM caused by Streptococcus pneumonia (n = 14), Neisseria meningitidis (n = 22), and Haemophilus influenza (n = 9). Methods. CSF inflammatory parameters, including cytokines and chemokines, MMP-9, and nitric oxide synthase activity, were assessed in a cohort of patients with BM from Burkina Faso. Results. Pneumococcal meningitis was associated with significantly higher CSF concentrations of IFN-?, MCP-1, and the matrix-metalloproteinase (MMP-) 9. In patients with a fatal outcome, levels of TNF-?, IL-1?, IL-1RA, IL-6, and TGF-? were significantly higher. Conclusion. The signature of pro- and anti-inflammatory mediators and the intensity of inflammatory processes in CSF are determined by the bacterial pathogen causing bacterial meningitis with pneumococcal meningitis being associated with a higher case fatality rate than meningitis caused by N. meningitidis or H. influenzae.
Grandgirard, Denis; Gaumann, Rahel; Coulibaly, Boubacar; Dangy, Jean-Pierre; Sie, Ali; Junghanss, Thomas; Schudel, Hans; Pluschke, Gerd; Leib, Stephen L.
Bacterial meningitis due to Streptococcus pneumoniae is associated with a significant mortality rate and persisting neurologic sequelae including sensory-motor deficits, seizures, and impairments of learning and memory. The presence of proliferating bacteria within the subarachnoid and ventricular space compartments triggers an intense inflammatory host response at killing the invading microorganism. Proinflammatory mediators released in the process include tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-6. TNF-alpha have several effects, including cytotoxicity, antiviral activity, transcription factor activation, and immune response regulation. Thus, the aim of this study was to verify the levels of the TNF-alpha after pneumococcal meningitis in male Wistar rats. The animals underwent a magna cistern tap receiving either 10 microL sterile saline as a placebo or an equivalent volume of a S. pneumoniae suspension at the concentration 5 x 10(9)cfu/mL. The animals were killed at 0, 6, 12, 24, 48 and 96 h after induction. The brain was removed and hippocampus, cortex, prefrontal and cerebrospinalfluid (CSF) were isolated and used for the determination of TNF-alpha levels. We found an increase in TNF-alpha levels at 6h after induction of the meningitis in the hippocampus (p<0.01), frontal cortex (p<0.05), and cerebrospinalfluid (p<0.001).There was no alteration in the cortex. Our data suggest that TNF-alpha is involved in the pathophysiology of the pneumococcal meningitis and could be investigated as a putative biomarker for brain damage in the first hours. PMID:19835931
Barichello, Tatiana; dos Santos, Ivonete; Savi, Geovana D; Florentino, Anelise F; Silvestre, Cintia; Comim, Clarissa M; Feier, Gustavo; Sachs, Daniela; Teixeira, Mauro M; Teixeira, Antonio L; Quevedo, João
Tuberculous meningitis (TBM) is the most common form of chronic infection of the central nervous system. Despite the magnitude of the problem, the general diagnostic outlook is discouraging. Specifically, there is no generally accepted early confirmative diagnosis protocol available for TBM. Various Mycobacterium tuberculosis antigens are now recognized as potential markers for diagnosis of TBM. However, their presence remains questionable, and many of these antigens are reported in the blood but not in the cerebrospinalfluid (CSF). This study identifies a specific protein marker in CSF which will be useful in early diagnosis of TBM. We have demonstrated the presence of a 30-kDa protein band in CSF of 100% (n = 5) of confirmed and 90% (n = 138) of suspected TBM patients out of 153 TBM patients. The 30-kDa band was excised from the gel, destained extensively, and digested with trypsin. The resulting peptides were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Partially purified proteins from CSF samples of TBM were analyzed by two-dimensional polyacrylamide gel electrophoresis and Western blotting. Immunoblotting and enzyme-linked immunosorbent assay (ELISA) were performed to confirm the presence of proteins in the 30-kDa protein band. The antigen 85 (Ag 85) complex was detected in CSF of TBM patients by indirect ELISA using antibodies against Ag 85 complex. The results of this study showed the 30-kDa protein band contained MTB proteins Rv3804c (Ag85A) and Rv1886c (Ag 85B), both members of the Ag85 complex. This was also confirmed by using immunotechniques such as indirect ELISA and the dot immunobinding assay. Detection of Ag85 complex was observed in CSF of 89% (71 out of 80) of suspected TBM patients that were 30-kDa protein positive. The observed 30-kDa protein in the CSF is comprised of the MTB Ag85 complex. This protein was earlier reported to be present in the blood of patients with extra-central nervous system tuberculosis. Therefore, this finding suggests that this protein can be used as a molecular marker for any type of tuberculous infection. It also provides a more sensitive immunoassay option for the early and confirmatory diagnosis of TBM. PMID:15939750
Kashyap, Rajpal S; Dobos, Karen M; Belisle, John T; Purohit, Hemant J; Chandak, Nitin H; Taori, Girdhar M; Daginawala, Hatim F
BACKGROUND: The central nervous system is considered a sanctuary site for HIV-1 replication. Variables associated with HIV cerebrospinalfluid (CSF) viral load in the context of opportunistic CNS infections are poorly understood. Our objective was to evaluate the relation between: (1) CSF HIV-1 viral load and CSF cytological and biochemical characteristics (leukocyte count, protein concentration, cryptococcal antigen titer); (2) CSF
Diego M Cecchini; Ana M Cañizal; Haroldo Rojas; Alicia Arechavala; Ricardo Negroni; María B Bouzas; Jorge A Benetucci
Abstract The presence of leukemic blasts detected by light microscopy in cerebrospinalfluid (CSF) establishes the diagnosis of leukemic meningitis in acute lymphoblastic leukemia/lymphoma (ALL). Flow cytometry immunophenotyping (FCI) is a very sensitive method that detects a minute number of aberrant cells, and is increasingly performed on CSF samples. We sought to determine the sensitivity and specificity of CSF FCI for the diagnosis of leukemic meningitis in ALL. Between November 2007 and August 2011, 800 CSF samples from 80 patients with ALL were available from diagnostic lumbar punctures (LPs; n = 80), follow-up LPs (n = 687) and at the time of relapse (n = 33). FCI was performed on 267 samples, and only identified aberrant cells in cytologically confirmed cases of leukemic meningitis. A blinded review of all cases with detectable CSF nucleated cells confirmed these findings. We conclude that CSF FCI has a 100% sensitivity and specificity for the detection of lymphoblasts. However, additional studies are needed to define the role this procedure plays in the diagnosis of leukemic meningitis. PMID:24134778
Mitri, Zahi; Siddiqui, Momin T; El Rassi, Fuad; Holden, Jeannine T; Heffner, Leonard T; Langston, Amelia; Waller, Edmund K; Winton, Elliott; McLemore, Morgan; Bernal-Mizrachi, Leon; Jaye, David; Arellano, Martha; Khoury, Hanna Jean
Introduction Making a differential diagnosis between bacterial meningitis and aseptic meningitis is a critical clinical problem. The utility of a cerebrospinalfluid (CSF) lactate assay for this purpose has been debated and is not yet routinely clinically performed. To adequately evaluate this assay, a systematic review and meta-analysis of studies of the CSF lactate concentration as a marker for both bacterial meningitis and aseptic meningitis was performed. Methods Electronic searches in PubMed, Scopus, the MEDION database and the Cochrane Library were conducted to identify relevant articles published before March 2009. A manual search of reference lists from selected articles was also conducted. Two reviewers independently selected relevant articles and extracted data on study characteristics, quality and accuracy. Results Twenty-five articles were identified that met the eligibility criteria. Diagnostic odds ratios were considerably homogenous (Chi-square P = 0.1009, I2 = 27.6%), and the homogeneity was further confirmed by a Galbraith plot and meta-regression analysis using several covariates. The symmetrical summary receiver-operator characteristic curve (SROC), fitted using the Moses-Shapiro-Littenberg method, was positioned near the upper left corner of the SROC curve. The Q value and area under the curve were 0.9451 and 0.9840, respectively, indicating excellent accuracy. The diagnostic accuracy of the CSF lactate concentration was higher than those of other four conventional markers (CSF glucose, CSF/plasma glucose quotient, CSF protein, and CSF total number of leukocytes) using a head to head meta-analysis of the 25 included studies. Conclusions To distinguish bacterial meningitis from aseptic meningitis, CSF lactate is a good single indicator and a better marker compared to other conventional markers.
A micellar electrokinetic chromatography (MEKC) method with ultraviolet detection at 280 nm is described for analysis of ciprofloxacin in cerebrospinalfluid (CSF) by direct injection without sample pretreatment. The proposed method was applied in one tuberculosis meningitis patient monitoring the concentration of ciprofloxacin in CSF after oral administration of 500 mg of ciprofloxacin after 12 hr. The separation of ciprofloxacin from the CSF
We report the case of a teenager with chronic lymphocytic meningitis for whom Tropheryma whipplei 16S rRNA PCR results were positive in two cerebrospinalfluid samples and one duodenal biopsy specimen. PCR targeting another specific sequence of Tropheryma whipplei and sequencing of the initially amplified 16S rRNA fragment did not confirm the results.
Goyo, Daniel; Camacho, Ana; Gomez, Carmen; de las Heras, Rogelio Simon; Otero, Joaquin R.; Chaves, Fernando
Single-dose pharmacokinetics of ceftriaxone were determined in 19 patients with proven bacterial meningitis. The dosage was 50 mg of ceftriaxone per kg. The plasma concentration time curve declined in a biexponential manner. The mean peak plasma concentration was 207 micrograms/ml, and the elimination half-life was 4 h. In 12 patients, multiple-dose pharmacokinetics were determined after a loading dose of 75 mg of ceftriaxone per kg, followed by 50-mg/kg doses every 8 h in 5 patients or every 12 h in 7 patients. The mean peak plasma concentration was 230 micrograms/ml after the first dose and 263 micrograms/ml after the last dose. Of 12 patients, 5 had trough values that were larger after multiple doses than after a single dose. Mean penetration of ceftriaxone into cerebrospinalfluid was 3.1%. The median cerebrospinalfluid bactericidal titer against the patients pathogens was greater than 1:1,024 and less than 1:2,048. The drug was well tolerated without adverse effects.
Del Rio, M; McCracken, G H; Nelson, J D; Chrane, D; Shelton, S
To study the cerebrospinalfluid (CSF) protein profiles of tuberculous meningitis (TBM) and discover potential biomarkers for TBM, differential expression of proteins in the CSF of patients with TBM, patients with cryptococcal meningitis, and a control group were compared using isobaric tags for relative and absolute quantitation labelling (iTRAQ) coupled with 2-dimensional liquid chromatography-tandem mass spectrometry (LC-MS). As a result, a total of 208 unique proteins with a molecular weight ranging from 10 KD to 135 KD were identified and quantified in CSF samples from patients with TBM. Of the proteins, 9 were expressed at levels differing 2.0 fold, 6 were up-regulated, and 3 were down-regulated. These proteins appear to be involved in calcium ion binding, lipoprotein metabolism, immune response, and signal conduction. Two differentially expressed proteins were identified using ELISA. The present study represents the successful use of iTRAQ to examine CSF from patients with TBM. The differentially expressed proteins identified may be potential diagnostic biomarkers and provide valuable insight into the underlying mechanisms of TBM. This study also demonstrated that the differential protein profiles of diseases can be quickly determined using iTRAQ-LC-MS, a potential method for quantitative comparative proteomics. PMID:24056169
Rifampin given orally was found to cross the blood-brain barrier, and was comparable to ethamputol in the treatment of tuberculous meningitis. Due to the difficulty of administering oral therapy, as most of the patients are unable to swallow properly, int...
I. A. Mikhail N. I. Girgis A. L. Bourgeois C. R. Lissner
We have recently described the induction of anti-cytokine autoantibodies (Aabs) in the serum as a novel mechanism for cytokine regulation during bacterial infections. Here we use the infant rat-model of Haemophilus influenzae type b (Hib) meningitis to examine the induction of five potentially important cytokines and their autoantibody responses in the CSF. Protein levels of the cytokines interferon-gamma (IFN-?), tumour necrosis factor-alpha (TNF-?), transforming growth factor-beta (TGF-?), IL-4 and IL-10 were detected at day 3 post-inoculation (p.i.) with maximum induction at day 8. Thereafter, these levels of cytokines had become undetectable. Increased Aab titres to these cytokines, except IL-4, were registered with peak levels between days 7 and 9. Upon re-inoculation with Hib at day 30, regeneration of Aabs was recorded 7 days later (i.e. at day 37). To control the specificity of these Aabs, preincubation of the CSF with a cytokine inhibited the binding effects of that particular cytokine, but not those of any other cytokine. Aabs dose-dependently inhibited IFN-?-induced MHC expression by peritoneal macrophages and TNF-?-mediated L929 cytotoxicity. Our data demonstrate for the first time the existence of the anti-cytokine antibodies in the CSF of the meningitis Hib model. Furthermore, the data present a role for the Aabs in cytokine regulation, which is consistent with the previously demonstrated effects of the Aabs in the serum.
BAKHIET, M; MUSTAFA, M; ZHU, J; HARRIS, R; LINDQUIST, L; LINK, H; DIAB, A
1. Eleven patients undergoing lumbar discectomy received cloxacillin by continuous i.v. infusion, starting before the operation. During the operation several blood samples and one CSF sample were taken. 2. Mean rate constants describing the passive transfer of drug from plasma to CSF (kp) and the largely active transfer in the opposite direction (kCSF) were estimated. 3. In some subjects the CSF albumin quotient, defined as the ratio between the albumin concentration in CSF and in plasma times 1000, was slightly elevated (up to 23) which caused a significant increase in the value of kp. 4. The estimate of mean kp for healthy individuals was 0.065 h-1, which corresponds to a half-life of 10 h. The estimate of mean kCSF was 2.10 h-1. This predicts a steady-state CSF drug concentration which is 3% of the unbound plasma drug concentration. 5. There was a significant lag between the time courses of plasma and CSF drug concentrations, presumably reflecting the time for drug to move from the choroid plexus to the lumbar sampling site. 6. Four other patients received cloxacillin for prophylactic or therapeutic reasons by continuous i.v. infusion. In three of those patients the albumin quotient was normal or slightly elevated and the steady-state CCSF/Cu ratio was similar to the predicted normal value. 7. These findings indicate that eradicating staphylococci from CSF in cases of meningitis with a low degree of inflammation may be difficult.
Schievink, H I; Mattie, H; Thomeer, R T; Van Strijen, E
We have evaluated the use of a broad-range PCR aimed at the 16S rRNA gene in detecting bacterial meningitis in a clinical setting. To achieve a uniform DNA extraction procedure for both gram-positive and gram-negative organisms, a combination of physical disruption (bead beating) and a silica-guanidiniumthiocyanate procedure was used for nucleic acid preparation. To diminish the risk of contamination as much as possible, we chose to amplify almost the entire 16S rRNA gene. The analytical sensitivity of the assay was approximately 1 × 102 to 2 × 102 CFU/ml of cerebrospinalfluid (CSF) for both gram-negative and gram-positive bacteria. In a prospective study of 227 CSF samples, broad-range PCR proved to be superior to conventional methods in detecting bacterial meningitis when antimicrobial therapy had already started. Overall, our assay showed a sensitivity of 86%, a specificity of 97%, a positive predictive value of 80%, and a negative predictive value of 98% compared to culture. We are currently adapting the standard procedures in our laboratory for detecting bacterial meningitis; broad-range 16S ribosomal DNA PCR detection is indicated when antimicrobial therapy has already started at time of lumbar puncture or when cultures remain negative, although the suspicion of bacterial meningitis remains.
Schuurman, Tim; de Boer, Richard F.; Kooistra-Smid, Anna M. D.; van Zwet, Anton A.
The aim of the study was to evaluate dynamics of selected acute phase proteins in serum and cerebrospinalfluid (CSF) in children with viral meningitis and to assess diagnostic power of protein determination for detection and treatment monitoring. 51 children with viral meningitis caused by ECHO 30 virus were included in the study group. Concentration of C-reactive protein (CRP), alpha 1-antitrypsin (AAT), alpha1-acid glycoprotein (AAG), alpha2-haptoglobin (HPT) and C3 complement fragment were determined in serum and CSF at entry and at day 14 after admittance to hospital. Control group for serum determination consisted in 30 healthy children (Group K1) and control group for CSF determination consisted in 19 hospitalized children in whom the diagnosis of meningitis was not confirmed (group K2). The greatest rise of acute phase proteins concentration was observed in children in case of HPT, AAG and C3 complement when determined in serum. Meningitis in children that was caused by ECHO 30 virus produces slight acute phase reaction that is more evident in serum than in CSF. It is confirmed by remarkable increase of AAG, HPT, C3 complement in serum and HPT in CSF either at entry or at the day 14. The determination of AAG, HPT and C3 complement in serum have diagnostic power that is strong enough to meningitis diagnostics and monitoring of treatment. PMID:15517816
Cerebrospinalfluid (CSF) samples from clinically diagnosed patients with detectable Angiostrongylus canto-nensis-specific antibodies (n = 10), patients with clinically suspected cases that tested negative for A. cantonensis-an-tibodies (n = 5) and patients with cerebral gnathostomiasis (n = 2) and neurocysticercosis (n = 2) were examined by a single-step polymerase chain reaction (PCR) method using the AC primers for the 66-kDa native protein gene. The PCR method detected A. cantonensis DNA in CSF samples from four of 10 serologically confirmed angiostrongyliasis cases. The PCR results were negative for the remaining CSF samples. The nucleotide sequences of three positive CSF-PCR samples shared 98.8-99.2% similarity with the reference sequence of A. cantonensis. These results indicate the potential application of this PCR assay with clinical CSF samples for additional support in the confirmation of eosinophilic meningitis due to A. cantonensis.
Interferon-?-induced GTPases are key to the protective immunity against microbial and viral pathogens. As yet, the cell interior has been regarded as the exclusive residence of these proteins. Here we show that a member of this group, human guanylate binding protein-1 (hGBP-1), is secreted from cells. Secretion occurred in the absence of a leader peptide via a nonclassical, likely ABC transporter-dependent, pathway, was independent of hGBP-1 GTPase activity and isoprenylation, and did not require additional interferon-?-induced factors. Interestingly, hGBP-1 was only secreted from endothelial cells but not from any of the nine different cell types tested. Clinically most important was the detection of significantly (P < 0.001, Mann-Whitney U-test) increased hGBP-1 concentrations in the cerebrospinalfluid of patients with bacterial meningitis (n = 32) as compared to control patients (n = 74). In this first report of a secreted GTPase, we demonstrate that secreted hGBP-1 may be a useful surrogate marker for diagnosis of bacterial meningitis.
Daptomycin monotherapy was superior to ceftriaxone monotherapy and was highly efficacious in experi- mental pneumococcal meningitis, sterilizing the cerebrospinalfluid (CSF) of three of three rabbits after 4 to 6 h. With daptomycin therapy only a negligible release of (3H)choline as marker of cell wall lysis was detectable in the CSF, peaking around 250 cpm\\/min after 4 h, compared to
A. Stucki; M. Cottagnoud; V. Winkelmann; T. Schaffner; P. Cottagnoud
Cerebrospinalmeningitis (CSM) is one of the infectious diseases likely to be affected by climate change. Although there are a few studies on the climate change-CSM nexus, none has considered perceptions of community members. However, understanding public perception in relation to a phenomenon is very significant for the design of effective communication and mitigation strategies as well as coping and adaptation strategies. This paper uses focus group discussions (FGDs) to fill this knowledge lacuna. Results show that although a few elderly participants ascribed fatal causes (disobedience to gods, ancestors, and evil spirits) to CSM infections during FGDs, majority of participants rightly linked CSM infections to dry, very hot and dusty conditions experienced during the dry season. Finally, community members use a suite of adaptation options to curb future CSM epidemics.
Cerebrospinalmeningitis (CSM) is one of the infectious diseases likely to be affected by climate change. Although there are a few studies on the climate change-CSM nexus, none has considered perceptions of community members. However, understanding public perception in relation to a phenomenon is very significant for the design of effective communication and mitigation strategies as well as coping and adaptation strategies. This paper uses focus group discussions (FGDs) to fill this knowledge lacuna. Results show that although a few elderly participants ascribed fatal causes (disobedience to gods, ancestors, and evil spirits) to CSM infections during FGDs, majority of participants rightly linked CSM infections to dry, very hot and dusty conditions experienced during the dry season. Finally, community members use a suite of adaptation options to curb future CSM epidemics. PMID:25003550
Tuberculous meningitis (TM) is the deadliest form of tuberculosis. Nearly two-thirds of HIV infected patients with TM die, and most deaths occur within one month. Current treatment of TM involves the use of drugs with poor penetration into the cerebro-spinalfluid (CSF). In this study, we present the mortality before and after implementing a new antituberculous regimen (ATR) with a higher drug penetration in CSF than the standard ATR during the initial treatment of TM in an HIV cohort study. The new ATR included levofloxacin, ethionamide, pyrazinamide, and a double dose of rifampicin and isoniazid and was given for a median of 7 days (interquartile range 6–9). The new ATR was associated with an absolute 21.5% (95% confidence interval (CI), 7.3–35.7) reduction in mortality at 12 months. In multivariable analysis, independent factors associated with mortality were the use of the standard ATR versus the new ATR (hazard ratio 2.05; 95% CI, 1.2–3.5), not being on antiretroviral therapy, low CD4 lymphocyte counts, and low serum albumin levels. Our findings suggest that an intensified initial ATR, which likely results in higher concentrations of active drugs in CSF, has a beneficial effect on the survival of HIV-related TM.
Cryptococcus neoformans is a fungal pathogen that encounters various microenvironments during growth in the mammalian host, including intracellular vacuoles, blood, and cerebrospinalfluid (CSF). Because the CSF is isolated by the blood-brain barrier, we hypothesize that CSF presents unique stresses that C. neoformans must overcome to establish an infection. We assayed 1,201 mutants for survival defects in growth media, saline, and human CSF. We assessed CSF-specific mutants for (i) mutant survival in both human bronchoalveolar lavage (BAL) fluid and fetal bovine serum (FBS), (ii) survival in macrophages, and (iii) virulence using both Caenorhabditis elegans and rabbit models of cryptococcosis. Thirteen mutants exhibited significant survival defects unique to CSF. The mutations of three of these mutants were recreated in the clinical serotype A strain H99: deletions of the genes for a cation ATPase transporter (ena1?), a putative NEDD8 ubiquitin-like protein (rub1?), and a phosphatidylinositol 4-kinase (pik1?). Mutant survival rates in yeast media, saline, and BAL fluid were similar to those of the wild type; however, survival in FBS was reduced but not to the levels in CSF. These mutant strains also exhibited decreased intracellular survival in macrophages, various degrees of virulence in nematodes, and severe attenuation of survival in a rabbit meningitis model. We analyzed the CSF by mass spectrometry for candidate compounds responsible for the survival defect. Our findings indicate that the genes required for C. neoformans survival in CSF ex vivo are necessary for survival and infection in this unique host environment.
Lee, Anthony; Toffaletti, Dena L.; Tenor, Jennifer; Soderblom, Erik J.; Thompson, J. Will; Moseley, M. Arthur; Price, Michael; Perfect, John R.
Zinc modulates the activity of glutamic acid decarboxylase, the rate limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter. Low cerebrospinalfluid GABA values have been reported in association with several seizure disorders, including febrile convulsions. It is also known that fever and/or infections may cause a reduction in serum zinc concentrations. In this study the hypothesis that febrile convulsions are related to low cerebrospinalfluid zinc was tested. Cerebrospinalfluid zinc concentrations were measured in 66 febrile children: 32 with febrile convulsions, 18 with fever but without convulsions, and 16 with aseptic (viral) meningitis. There was no statistically significant difference in the cerebrospinalfluid zinc between the three groups of children, and the mean concentration was 26.2 micrograms/l. No significant relationship was found between either age, gender, maximal temperature, type of infection, or time of performance of the lumbar puncture and cerebrospinalfluid zinc concentration. These results do not support the hypothesis that febrile convulsions are related to reduced cerebrospinalfluid zinc concentrations.
Garty, B Z; Olomucki, R; Lerman-Sagie, T; Nitzan, M
The presence of apolipoproteins A-I, E, C-II, and C-III and the absence of apolipoprotein B was demonstrated in human cerebrospinalfluid. The concentration of apolipoproteins was measured by electroimmunoassay. Apolipoproteins E, C-II, and C-III were present in cerebrospinalfluid at 3--5% of their concentration in plasma; the cerebrospinalfluid level of apolipoprotein A-I was 0.4%. Most of the cerebrospinalfluid apolipoproteins were present in the rho less than 1.21 g/ml lipoprotein fraction. The major apolipoporteins of cerebrospinalfluid are E and A-I. The possible mechanism of transfer and the physiological and pathophysiological role of apolipoproteins in cerebrospinalfluid are postulated. Images
Cerebrospinalfluid (CSF) shunt technology has undergone rapid advances in the past two decades. As a result, pediatricians and other primary care physicians are being asked with increasing frequency to provide care for persons with CSF shunts. Familiarity with the more common shunts is a prerequisite to intelligent management of shunt related problems. Physicians providing daily care must have carefully documented hospital records and operative notes available to them as well as information detailing the safe evaluation of shunt patency and function if they are to manage patients with CSF shunts properly. In addition, parents and guardians must be alerted to signs and symptoms related to shunt malfunction. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 7.Figure 8.
SUMMARY: Quantitative real-time reverse transcription-polymerase chain reaction (q-RT-PCR) was used to diagnose echovirus infection and the results were compared to those obtained with the viral culture rate. Cerebro- spinal fluid (CSF) from a total of 40 aseptic meningitis patients was used. Positive CSF samples, determined by viral culture (n = 29), contained significantly higher echovirus genome copy numbers (mean, 329
A 4-year-old tearing child with obstruction of the nasolacrimal duct was treated with dacryocystorhinostomy three years after naso-orbital injury. However, what appeared to be tearing persisted, and meningitis developed. Coronal CT scans demonstrated traumatic encephalocele of the posterior superior orbital roof. A chronic orbital cerebrospinalfluid (CSF) leak was diagnosed. To our knowledge no case of chronic CSF leak has been reported that simulated tearing in an otherwise asymptomatic child. In the tearing patient who has a naso-orbital fracture the possibility of chronic CSF leak should be considered. Images
Cerebrospinalfluid gamma-aminobutyric acid (CSF-GABA) was analysed by radioreceptor assay in 16 normal controls and 84 patients with various neurological and psychiatric diseases. In patients with spinocerebellar degeneration, neuro-Behçet's syndrome and Parkinson's disease, CSF-GABA levels were decreased. On the other hand, increased CSF-GABA levels were detected in patients with meningitis.
Kuroda, H; Ogawa, N; Yamawaki, Y; Nukina, I; Ofuji, T; Yamamoto, M; Otsuki, S
This study examined the isoenzymatic pattern of LDH in the cerebrospinalfluid (CSF) as well as the ratio between the five fractions of LDH among patients with various brain tumours, carcinomatous meningitis and control groups. LDH 1/LDH 2 less than 1 was found significant for carcinomatous meningitis (p less than 0.001) and brain metastases (p less than 0.001). LDH 1/LDH 2 ratio was found to be significantly lower in carcinomatous meningitis than in brain metastases (p less than 0.05). No LDH 1/LDH 2 ratios smaller than 1 were found in the other groups. The LDH 1/LDH 2 ratio smaller than 1 was found in the early stage of carcinomatous meningitis without other evidences of the involvement of the leptomeninges. Examination of LDH 1/LDH 2 can be found as an adjunctive method to identify brain metastases and carcinomatous meningitis at the initial stage.
We report the development of a nested-PCR-based assay for the detection of Cryptococcus neoformans in cerebrospinalfluid. The specificity and sensitivity of the test were assessed. The technique was then applied to 40 cerebrospinalfluid samples. We obtained positive reactions for all 21 clinical samples from patients who had been previously diagnosed as having cryptococcal meningitis by conventional techniques and
PAOLA RAPPELLI; RICCARDO ARE; GIUSEPPE CASU; PIER LUIGI FIORI; PIERO CAPPUCCINELLI; ANTONIO ACETI
Abstracts Background Meningitis is an important cause of morbidity and mortality in low-resource settings. In sub-Saharan Africa, the meningitis belt has been characterized by particularly high and seasonal incidences of bacterial meningitis extending throughout life. Despite the progress being made in treating the condition, the mortality rates continue to be high, ranging between 2% and 30% globally. In Ghana, the mortality rate of meningitis has been estimated to range from 36% to 50%. However little information is available on the pathogens contributing to meningitis and their antimicrobial susceptibilities. Updated information is essential to adjust the recommendations for empirical treatment or prevention of meningitis which could have immense implications for local and global health. Methods We retrospectively reviewed laboratory records of all patients suspected of bacterial meningitis who underwent a lumbar puncture from January 1, 2008 to December 31, 2010. Data were retrieved from laboratory record books and double entered into a Microsoft® excel spreadsheet. Results Records of 4,955 cerebrospinalfluid samples were analysed. Of these, 163 (3.3%, 95%CI: 2.8% to 3.8%) were confirmed meningitis and 106 (2.1%, 95%CI: 1.7% to 2.6%) were probable meningitis cases. Confirmed meningitis cases were made up of 117 (71.8%) culture positive bacteria, 19 (11.7%) culture positive Cryptococcus neoformans and 27(16.6%) Gram positive bacteria with negative culture. The most prevalent bacteria was Streptococcus pneumoniae 91 (77.7%), followed by E.coli 4 (3.4%), Salmonella species 4 (3.4%), Neisseria meningitidis 3 (2.5%), Pseudomonas species 3(2.5%) and others. Pneumococcal isolates susceptibility to penicillin, chloramphenicol and ceftriaxone were 98.9% (95%CI: 94.0% to 100.0%), 83.0% (95%CI: 73.4% to 90.1%) and 100.0% (95%CI: 95.8% to 100.0%) respectively. Conclusion Streptococcus pneumoniae is an important cause of meningitis among all age groups and its susceptibility to penicillin and ceftriaxone still remains very high. Ghanaians of all ages and possibly other developing countries in the meningitis belt could benefit from the use of the pneumococcal vaccine. Other bacterial and fungal pathogens should also be considered in the management of patients presenting with meningitis.
Examination of human cerebrospinalfluid (CSF) has been performed for over 100 years. Since CSF is in direct contact with\\u000a the extracellular surface of the brain, the biochemical composition of this fluid is altered in disorders related to the central\\u000a nervous system. Hence, it is of great interest to investigate thoroughly the human CSF proteome, to identify proteins, and\\u000a to
To determine the involvement of human cytomegalovirus (CMV) in conditions of neurological impairment, detection of CMV DNA was attempted in cerebrospinalfluid obtained from 45 neurologically affected children aged from 1 month to 17 years by means of the polymerase chain reaction. Four patients (congenital CMV encephalopathy with West's syndrome, acute encephalitis, chronic epileptic encephalopathy, and lissencephaly) had CMV DNA in their cerebrospinalfluid. CMV DNA was absent in the cerebrospinalfluid of 11 neurologically unaffected controls aged from 1 month to 11 years. Three patients with acute CMV hepatitis had no CMV DNA in their cerebrospinalfluid. Among the four patients who had CMV DNA in their cerebrospinalfluid, two did not excrete CMV DNA or CMV antigen in the urine. The possible pathogenetic significance of CMV DNA in the cerebrospinalfluid is discussed. By applying the polymerase chain reaction to cerebrospinalfluid, the mode of brain invasion by CMV can be clarified further. Images
Kohyama, J; Kajiwara, M; Shimohira, M; Iwakawa, Y; Okawa, H
Bacterial colonization of cerebrospinalfluid shunts is a cause of significant morbidity, causing not only shunt malfunction\\u000a and chronic ill-health but has also been implicated in an immune-complex glomerulonephritis. Almost all shunt colonizations\\u000a involve Staphylococcus albus which gains access to the shunt during surgery and grows in microcolonies inside the shunt. The\\u000a most reliable means of diagnosis at present is
We report, in a clinical setting, the tigecycline concentration and area under the concentration-time curve (AUC) - both in blood and in cerebrospinalfluid (CSF) - of a patient with a ventriculo-atrial shunt infection. Tigecycline weakly penetrates CSF the CSF-to-serum concentration ratio was 0.079 and CSF-to-serum AUC(0-12) ratio was 0.067. PMID:24131423
Pallotto, Carlo; Fiorio, Maurizio; D'Avolio, Antonio; Sgrelli, Alessio; Baldelli, Franco; Di Perri, Giovanni; De Socio, Giuseppe Vittorio
In this work, changes in the cerebrospinalfluid in acute and chronic polyneuritis as well as in the Guillan-Barré-Strohl syndrome are discussed and and it is pointed out that a specific coordination of the inflammatory cerebrospinalfluid syndromes to certain pathogens or noxae cannot be made. For the differentiation of the Guillain-Barré-Strohl syndrome and existence of increased gamma-globulin bands with identical mobility in the serum is pointed out. In myelitic disease pictures, acute and chronic cerebrospinalfluid syndromes are distinguished also in the cerebrospinalfluid according to the clinical course; regular changes, however, cannot be derived. Syphilitic cerebrospinal-fluid syndromes can easily be differentiated by their immunoactive findings. In multiple sclerosis, we distinguish between typical and atypical changes in the cerebrospinalfluid. Above all, the oligoclonal bands, i. e. the discontinuous proceeding of the gamma-globulin zone and the existence of several bands in the agar gel electrophoresis, play an essential role. In 95 per cent of the cases, oligoclonal bands can be shown. There are no greater differences with respect to oligoclonal bands between intermittent and chronic-progressive courses. For the differential diagnosis of haemorrhagic syndromes, the cerebrospinalfluid cell picture can make a considerable contribution. Macrophages loaded with erythrocytes indicate that a haemorrhage occurred 12 to 18 hours before; macrophages loaded with haemosiderin indicate a haemorrhage that occurred 6 to 8 days before; and macrophages loaded with erythrocytes and haemosiderin indicate a seeping haemorrhage or an event that occurred several times. The Nonne-Froin syndrome indicates a massive protein increase often with a regular or only slightly increased number of cells. The importance of the Queckenstedt tests is pointed out. A particular role is played by meningitis carcinomatosa et sarcomatosa with the demonstration of a great number of tumour cells. PMID:532463
Recurrent attacks of meningitis occurring independent of a systemic bacterial infection should be considered as a cerebrospinal leak either otorrhea or rhinorrhea. Three cases each with a different cause were diagnosed chiefly on the basis of the history and a bulging noninflammatory eardrum. Subsequent use of fluorescein intrathecally not only helped to confirm the diagnosis but was very useful at surgery in locating the leak in the dura of the oval window of the ear. Many materials have been used but autogenous temporal fascia or fascia lata seemed to be most effective in these cases. The sandwiching of the dura between two pieces of fascia is not only realistic but was found to be very effective. One piece of fascia between the arachnoid and dura and another between the dura and bone give a tight seal. PMID:703450
Effective use of specific vaccines to control epidemic cerebrospinalmeningitis requires early, precise etiologic diagnosis of cases. However, since the first cases often occur in areas remote from medical laboratories; etiologic diagnosis is seldom possi...
W. R. Sanborn M. Schlumberger Y. A. Alzouma R. Triau
Infections of cerebrospinalfluid shunts continue to be a substantial source of mortality and morbidity in children with hydrocephalus. Although several therapeutic modalities are currently used for the treatment of shunt infections, there are no clear guidelines for treatment. The purpose of this study was to determine the common pathogens of cerebrospinalfluid shunt infections and evaluate the success of
M. Turgut; D. Alabaz; F. Erbey; E. Kocabas; T. Erman; E. Alhan; N. Aksaray
Interferon was detected in the cerebrospinalfluid (CSF) of 26 of 51 children with aseptic meningitis, two of 44 with bacterial meningitis, and four of 118 with miscellaneous conditions including encephalitis, convulsive disorders and leukemia with neurological involvement. The geometric mean titre of interferon in mumps meningitis was seven to eight times higher than that in enteroviral meningitis; however, levels of interferon were not related to the concentration of leukocytes in CSF from these patients. Interferon titres were relatively greater at the height of the febrile response in children with mumps meningitis or enteroviral meningitis. There was no association between the presence of interferon in the CSF and the isolation of mumps virus or an enterovirus from the same specimen. Patients frequently developed homologous antibody one to three days after signs of aseptic meningitis, obscuring the relationship of interferon production to clinical improvement.
Spontaneous intracranial hypotension is a rare syndrome, characterized by pressure in the cerebrospinalfluid ranging between 50 and 70 mmH2O and postural headache. Its diagnosis is made through the clinical presentation, measurement of the cerebrospinalfluid pressure and neurorimage features. The clinical recognition of this pathology has been increasing and the differential diagnosis must be made with inflammatory meningeal processes and tumor. We report a case of spontaneous nerve root cerebrospinalfluid leaks in a 34 year-old man and intracranial hypotension. A literature review was performed evaluating the clinical, diagnostic and therapeutic aspects of this unusual pathology. PMID:12715038
Falavigna, Asdrubal; Ferraz, Fernando Antonio Patriani; Boscato, Giovana; Shimokawa, Marcos
The study was conducted on 16 strains of Acinetobacter sp. which were isolated from cerebrospinalfluid. The diagnostic material was analysed with the use of automatic BacT/Alert system (Organon Teknika). The analysis was performed in the Department of Microbiology, Medical University in Bydgoszcz. API 20NE system (bioMérieux) enabled the identification of 14 strains (87.5%) as A. baumannii, 1 strain as A. haemolyticus and 1 strain as A. lwoffii. The micro-organisms were isolated from patients whose age ranged between 4 and 66 years. These patients were treated in the departments of Neurosurgery (75.0%), Neurology (18.8%) and Intensive Therapy (6.2%). The infection of cerebrospinalfluid was caused by injury and subsequent exposure to the bacteria present in external environment. Antibiotic-sensitivity of these micro-organisms was evaluated with the help of disc-diffusion method, observing standardisation conditions outlined by NCCLS. All the strains proved sensitive to carbapenems, 15 strains were sensitive to netilmicin, 7 strains--to tobramycin and 7 strains--to amikacin. All the strains displayed multiple resistance. The only exception was A. haemolyticus. The use of two-discs allowed for the detection of ESBLs in 7 A. baumannii strains. Positive results were most frequently obtained after the combination of sublactam and aztreonam. Due to microscopic resemblance between Acinetobacter spp., and bacteria of Neisseria, Moraxella and Haemophilus genus, microbiological diagnostics should not be restricted to microscopic assessment of cerebrospinalfluid and quick serological tests evaluating the antigens of the most frequent aetiological factors. Considering multiple resistance of Acinetobacter spp. to antibiotics, the treatment should be based on sensitivity tests and the ability of a given antibiotic to penetrate into cerebrospinalfluid. In our opinion, both reasonable antibiotic policy as well as observing the principles of hygiene and monitoring infections play equally important roles in the prevention of infections with Acinetobacter spp. Such combined measures may help to prevent the spreading of multiple resistant strains in hospital environment. PMID:11208283
Gospodarek, E; Kra?nicki, K; Zió?kowski, G; Kasprzak, H; Beuth, W
The author analyzes a historical, long, and tortuous way to discover the cerebrospinalfluid. At least 35 physicians and anatomists described in the text have laid the fundamentals of recognition of this biological fluid's presence. On the basis of crucial anatomical, experimental, and clinical works there are four greatest physicians who should be considered as equal cerebrospinalfluid's discoverers: Egyptian Imhotep, Venetian Nicolo Massa, Italian Domenico Felice Cotugno, and French François Magendie. PMID:24396600
Background: Technological advances have made it possible to examine the human cerebrospinalfluid (CSF) in a manner that was previously impossible. CSF provides a window into the changes that occur in the central nervous system (CNS) in health and disease. Through analysis of the CSF, we discern indirectly the state of health of the CNS, and correctly or incorrectly, draw conclusions regarding mechanisms of CNS injury and repair. Objective, Materials and Methods: To review the current state of knowledge of changes in the CSF in multiple sclerosis. Discussion: Establishing CSF markers that permit evaluation of the various biological processes in multiple sclerosis remains a challenge. Of all the biological processes, inflammatory markers are probably the best identified. Detection of oligoclonal immunoglobulin bands in the CSF is now established as the single most useful laboratory marker in the CSF to aid in the diagnosis of multiple sclerosis. Markers of demyelination, remyelination, neuro-axonal loss, neural repair and regeneration, and astrogliosis are only now being recognized. A good surrogate for any of these pathophysiological processes has not been defined to date. Conclusion: The goal of future research is not only to define surrogate markers in the CSF for each of the above functions, but also to extend it to other more readily accessible body fluids like blood and urine. A synopsis of the current literature in most of these areas of CSF evaluation pertaining to multiple sclerosis is presented in this article.
In the past few years, application of the PCR to the detection of herpes simplex virus (HSV) DNA in the cerebrospinalfluid (CSF) from patients with encephalitis and meningitis has become standard laboratory practice. However, from an operational perspective, the true diagnostic value of PCR in this setting is yet to be realized because most laboratories subject the amplification products
YI-WEI TANG; PAUL N. RYS; BARBARA J. RUTLEDGE; P. SHAWN MITCHELL; THOMAS F. SMITH; DAVID H. PERSING
Eyes with normal-pressure glaucoma and those with high-pressure glaucoma can show a similar optic nerve head appearance, while eyes with vascular optic neuropathies show a markedly different optic disc appearance. Factors in addition to intraocular pressure (IOP) may thus play a role in the pathogenesis of glaucomatous optic neuropathy. Clinical and experimental studies showed that (1) physiologic associations between cerebrospinalfluid (CSF) pressure, systemic arterial blood pressure, IOP and body mass index exist; (2) a low CSF pressure was associated with the development of glaucomatous optic nerve damage in cats; (3) patients with normal (intraocular) pressure glaucoma had significantly lower CSF pressure and a higher trans lamina cribrosa pressure difference when compared to normal subjects; and (4) patients with normal- pressure glaucoma as compared with patients with high-pressure glaucoma have a significantly narrower orbital CSF space. A shallow orbital CSF space has been shown to be associated with a low CSF pressure. Due to anatomic reasons, the orbital CSF pressure and the optic nerve tissue pressure (and not the atmospheric pressure) form the retro-laminar counter-pressure against the IOP and are thus part of the trans-lamina cribrosa pressure difference and gradient. Assuming that an elevated trans-lamina cribrosa pressure difference and a steeper trans-lamina cribrosa pressure gradient are important for glaucomatous optic nerve damage, a low orbital CSF pressure would therefore play a role in the pathogenesis of normal-(intraocular) pressure glaucoma. Due to the association between CSF pressure and blood pressure, a low blood pressure could be indirectly involved.
A simple, easily operated, portable diagnostic kit, employing coagglutination reagents, has been developed for the rapid, bedside diagnosis of cerebrospinalmeningitis. Field trials using this kit were conducted in a rural area of sub-Saharan Africa for identifying the etiological agents of meningitis outbreaks. West African village medical attendants were taught to use this kit and succeeded in making rapid specific diagnoses of meningitis cases. Other acute infections such as cholera and typhoid fever can also be rapidly diagnosed in a similar manner. This rapid diagnostic system offers appropriate technology in support of primary health care delivery in the rural areas of developing countries. ImagesFig. 1
Clinical features and serial cerebrospinalfluid (CSF) samples of 50 patients who underwent myelography with iophendylate were studied. Forty two patients (84%) developed one or more features suggestive of meningism lasting for 2-4 days. There was significant rise in the average (mean) CSF counts from 9.81 in the premyelogram sample to 532.6 at the end of 24 hours (p less than 0.001). Both neutrophil and lymphocyte (p less than 000) count increased. At the end of one week, there was significant decrease of total cells in the CSF to 204 (p less than 0.001). Both, neutrophils and lymphocytes decreased. There was significant rise in total proteins in the 24 hours sample, but the fall at one week was not significant statistically. The sugar and chloride values did not change significantly. All CSF samples were negative for bacterial cultures. In conclusion, a significant proportion of the patients undergoing iophendylate myelography develop clinical features suggestive of meningeal irritation and change in the CSF fractions suggestive of meningitis: however these changes are transient and do not warrant institution of chemotherapy or steroids. PMID:1512716
Mehta, H J; Ramakantan, R; Piparia, D H; Hande, A M; Goel, A; Satoskar, A R; Dastur, F D
Congenital tegmental defects that present as unsuspected cerebrospinalfluid (CSF) otorrhea are diagnostic and therapeutic challenges. We reviewed 5 such patients to determine an optimal strategy for evaluation. Five patients presented with watery otorrhea, 4 of them after ventilation tube placement, and only 1 with rhinorrhea. The preoperative analysis of middle ear effusion for ?2-transferrin was positive in 2\\/4, equivocal
Hannu J. Valtonen; Carl A. Geyer; Edward C. Tarlov; Carl B. Heilman; Dennis S. Poe
Forty-eight patients with cerebrospinalfluid leaks comprise this retrospective study. There were 39 traumatic and 9 spontaneous leaks. Nine patients were initially managed with bed rest and spinal drainage, but 3 patients in this group ultimately required surgical intervention for repair of their persistent leaks. Thirty-nine patients had surgery as initial therapy, with 33 extracranial repairs, 2 intracranial repairs, and
Mark S. Persky; Stephen G. Rothstein; Stephen D. Breda; Noel L. Cohen; Paul Cooper; Joseph Ransohoff
Beta2-Microglobulin (?2-m) is a low molecular weight protein occurring in all body fluids. Its concentration increases in various pathologies. Increased values in cerebrospinalfluid (CSF) are ascribed to an activation of immune system. Using immunoturbidimetry, we examined concentrations of beta2-microglobulin in cerebrospinalfluid in a large group of 6274 patients with defined neurological diseases. Cell counts, total protein, albumin, glucose, lactic acid, immunoglobulins concentrations, and isofocusing (IEF) were also evaluated. We found substantial changes of CSF ?2-m concentrations in purulent meningitis, leptomeningeal metastasis, viral meningitis/encephalitis, and neuroborreliosis, while in multiple sclerosis these changes were not significant. Intrathecal synthesis and immune activation were present in these clinical entities. A new normative study enables better understanding of beta2-microglobulin behavior in CSF.
Svatonova, Jana; Borecka, Klara; Adam, Pavel; Lanska, Vera
Using a liquid chromatography-tandem mass spectrometry method, the serum and cerebrospinalfluid (CSF) concentrations of colistin were determined in patients aged 1 months to 14 years receiving intravenous colistimethate sodium (60,000 to 225,000 IU/kg of body weight/day). Only in one of five courses studied (a 14-year-old receiving 225,000 IU/kg/day) did serum concentrations exceed the 2 ?g/ml CLSI/EUCAST breakpoint defining susceptibility to colistin for Pseudomonas and Acinetobacter. CSF colistin concentrations were <0.2 ?g/ml but increased in the presence of meningitis (?0.5 ?g/ml or 34 to 67% of serum levels).
During acute Lyme disease, bacteria can disseminate to the central nervous system (CNS) leading to the development of meningitis and other neurologic symptoms. Here we have analyzed pooled cerebrospinalfluid (CSF) allowing a deep view into the proteome for patients diagnosed with early-disseminated Lyme disease and CSF inflammation. Additionally, we analyzed individual patient samples and quantified differences in protein abundance employing label-free quantitative mass spectrometry based methods. We identified 108 proteins that differ significantly in abundance in patients with acute Lyme disease from controls. Comparison between infected patients and control subjects revealed differences in proteins in the CSF associated with cell death localized to brain synapses and others that likely originate from brain parenchyma.
Angel, Thomas E.; Jacobs, Jon M.; Smith, Robert P.; Pasternack, Mark S.; Elias, Susan; Gritsenko, Marina A.; Shukla, Anil; Gilmore, Edward C.; McCarthy, Carol; Camp, David G.; Smith, Richard D.; Warren, H. Shaw
During acute Lyme disease, bacteria can disseminate to the central nervous system (CNS), leading to the development of meningitis and other neurologic symptoms. Here we have analyzed pooled cerebrospinalfluid (CSF) allowing a deep view into the proteome for patients diagnosed with early disseminated Lyme disease and CSF inflammation. Additionally, we analyzed individual patient samples and quantified differences in protein abundance employing label-free quantitative mass spectrometry-based methods. We identified 108 proteins that differ significantly in abundance in patients with acute Lyme disease from controls. Comparison between infected patients and control subjects revealed differences in proteins in the CSF associated with cell death localized to brain synapses and others that likely originate from brain parenchyma. PMID:22900834
Angel, Thomas E; Jacobs, Jon M; Smith, Robert P; Pasternack, Mark S; Elias, Susan; Gritsenko, Marina A; Shukla, Anil; Gilmore, Edward C; McCarthy, Carol; Camp, David G; Smith, Richard D; Warren, H Shaw
The brain and the spinal cord are contained in a cavity and are surrounded by cerebrospinalfluid (CSF), which provides physical\\u000a support for the brain and a cushion against external pressure. Hydrocephalus is a disease, associated with disturbances in\\u000a the CSF dynamics, which can be surgically treated by inserting a shunt or third ventriculostomy. This review describes the\\u000a physiological background,
Anders Eklund; Peter Smielewski; Iain Chambers; Noam Alperin; Jan Malm; Marek Czosnyka; Anthony Marmarou
The choroid plexus epithelium is a cuboidal cell monolayer, which produces the majority of the cerebrospinalfluid. The concerted action of a variety of integral membrane proteins mediates the transepithelial movement of solutes and water across the epithelium. Secretion by the choroid plexus is characterized by an extremely high rate and by the unusual cellular polarization of well-known epithelial transport proteins. This review focuses on the specific ion and water transport by the choroid plexus cells, and then attempts to integrate the action of specific transport proteins to formulate a model of cerebrospinalfluid secretion. Significant emphasis is placed on the concept of isotonic fluid transport across epithelia, as there is still surprisingly little consensus on the basic biophysics of this phenomenon. The role of the choroid plexus in the regulation of fluid and electrolyte balance in the central nervous system is discussed, and choroid plexus dysfunctions are described in a very diverse set of clinical conditions such as aging, Alzheimer's disease, brain edema, neoplasms, and hydrocephalus. Although the choroid plexus may only have an indirect influence on the pathogenesis of these conditions, the ability to modify epithelial function may be an important component of future therapies. PMID:24137023
Damkier, Helle H; Brown, Peter D; Praetorius, Jeppe
CEREBROSPINALFLUID rhinorrhoea is defined as the leakage of CEREBROSPINALFLUID through the nose due to communication between nasal cavity and Sub-arachnoid space. It occurs due to breach in 4 layers – mucosa of the nose and PNS, skull base, Duramater, Subarachnoid membrane. With the advent of nasal endoscope and advancement in technology, Endoscopic Endonasal closure of CEREBROSPINALFLUID leak has reached tremendous heights due to exact localization and precise placement of graft. In this article, we are publishing a case report of Non-traumatic normal pressure CEREBROSPINALFLUID leak of more than 1.5cm in size which was successfully closed Endoscopically by multilayered technique
R, Sumitha; Hari, P M; Kumar, S Ramya; Hariprasad, R
Analysis of cerebrospinalfluid (CSF) samples from normal sheep and from cases of some common neurological diseases revealed a significant increase (P less than 0.05) in the group mean CSF protein concentration for meningitis, listeriosis and spinal abscess but not for scrapie, spinal injury, ovine pregnancy toxaemia or polioencephalomalacia. The CSF white blood cell count (WBC) was significantly increased (P less than 0.05) in the meningitis group and in those cases of listeriosis which failed to respond to antibiotic therapy. All cases of bacterial infection of the central nervous system (CNS) could be identified by the combined interpretation of the protein concentration and the differential WBC count. It is concluded that CSF analysis is useful clinically in differentiating traumatic from infective spinal lesions and toxic or metabolic lesions from bacterial meningitis in sheep. PMID:1551009
A multi-centre randomised open trial was done to determine whether moderate oral fluid restriction or intravenous fluid at full maintenance volumes would result in a better outcome for children with bacterial meningitis in Papua New Guinea, and what clinical signs could guide fluid management. Children with clinical signs and cerebrospinalfluid suggestive of bacterial meningitis received either breast milk by nasogastric tube at 60% of normal maintenance volumes (n = 172) or intravenous half-normal saline and 5% dextrose at 100% of normal maintenance volumes (n = 174) for the 1st 48 hrs of treatment. An adverse outcome was death or severe neurological sequelae, and a good outcome was defined as intact survival or survival with at worst mild-to-moderate neurological sequelae. The probability of an adverse outcome was 24.7% in the intravenous group and 33.1% in the oral-restricted group, but the difference was not statistically significant (RR 0.75, 0.53-1.04, p = 0.08). Sunken eyes or reduced skin turgor at presentation were risk factors for an adverse outcome (OR 5.70, 95% CI 2.87-11.29) and were most strongly associated with adverse outcome in the fluid-restricted group. Eyelid oedema during treatment was also a risk factor for an adverse outcome (OR 2.54, 95% CI 1.36-4.75) and eyelid oedema was much more common in the intravenous group (26%) than in the restricted group (5%). For many children with bacterial meningitis in less developed countries, moderate fluid restriction is unnecessary and will be harmful; a normal state of hydration should be achieved but over-hydration should be avoided. Giving 100% of normal maintenance fluids, especially with intravenous hypotonic fluid, will lead to oedema in up to one quarter of children with bacterial meningitis. If additional intravenous fluids are required for children with meningitis, an isotonic solution should be used. PMID:12070950
Cerebrospinalfluid (CSF) fistulae can produce leakage through a defect in the bony skull and meninges into the contiguous air-filled cavities at the base of the skull. The major risk is central nervous system infection. When abundant clear rhinorrhea or otorrhea is present, the diagnosis is obvious and imaging is used to localize the fistula. Computed tomography (CT) with millimetric slices and magnetic resonance imaging (MRI) are the most effective diagnostic tools. CT cisternography, an invasive procedure, should only be used when the diagnosis remains uncertain following CT scan and MRI. When CSF leakage is sparse or intermittent, the diagnosis can be made by measuring beta-2 transferrine in the escaping fluid. CT scan followed by MRI are also useful for making the diagnosis and locating the fistula when exterior leakage is absent. CT scan alone is effective for assessing isolated otorrhea. If the diagnosis remains uncertain after all these studies have been used, the patient should be closely followed clinically and isotopic study or surgery should be considered. PMID:15026731
To identify unknown human viruses, we analyzed serum and cerebrospinalfluid samples from patients with unexplained paraplegia from Malawi by using viral metagenomics. A novel cyclovirus species was identified and subsequently found in 15% and 10% of serum and cerebrospinalfluid samples, respectively. These data expand our knowledge of cyclovirus diversity and tropism.
Zijlstra, Ed E; van Hellemond, Jaap J.; Schapendonk, Claudia M.E.; Bodewes, Rogier; Schurch, Anita C.; Haagmans, Bart L.; Osterhaus, Albert D.M.E.
The Parkinsonian disorders are a large group of neurodegenerative diseases including idiopathic Parkinson’s disease (PD) and atypical Parkinsonian disorders (APD), such as multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, and dementia with Lewy bodies. The etiology of these disorders is not known although it is considered to be a combination of genetic and environmental factors. One of the greatest obstacles for developing efficacious disease-modifying treatment strategies is the lack of biomarkers. Reliable biomarkers are needed for early and accurate diagnosis, to measure disease progression, and response to therapy. In this review several of the most promising cerebrospinal biomarker candidates are discussed. Alpha-synuclein seems to be intimately involved in the pathogenesis of synucleinopathies and its levels can be measured in the cerebrospinalfluid and in plasma. In a similar way, tau protein accumulation seems to be involved in the pathogenesis of tauopathies. Urate, a potent antioxidant, seems to be associated to the risk of developing PD and with its progression. Neurofilament light chain levels are increased in APD compared with PD and healthy controls. The new “omics” techniques are potent tools offering new insights in the patho-etiology of these disorders. Some of the difficulties encountered in developing biomarkers are discussed together with future perspectives.
According to the traditional understanding of cerebrospinalfluid (CSF) physiology, the majority of CSF is produced by the choroid plexus, circulates through the ventricles, the cisterns, and the subarachnoid space to be absorbed into the blood by the arachnoid villi. This review surveys key developments leading to the traditional concept. Challenging this concept are novel insights utilizing molecular and cellular biology as well as neuroimaging, which indicate that CSF physiology may be much more complex than previously believed. The CSF circulation comprises not only a directed flow of CSF, but in addition a pulsatile to and fro movement throughout the entire brain with local fluid exchange between blood, interstitial fluid, and CSF. Astrocytes, aquaporins, and other membrane transporters are key elements in brain water and CSF homeostasis. A continuous bidirectional fluid exchange at the blood brain barrier produces flow rates, which exceed the choroidal CSF production rate by far. The CSF circulation around blood vessels penetrating from the subarachnoid space into the Virchow Robin spaces provides both a drainage pathway for the clearance of waste molecules from the brain and a site for the interaction of the systemic immune system with that of the brain. Important physiological functions, for example the regeneration of the brain during sleep, may depend on CSF circulation.
Two-dimensional gel electrophoresis and peptide mass fingerprinting were used to identify proteins in cerebrospinalfluid (CSF) pooled from three patients with multiple sclerosis (MS) and in CSF pooled from three patients with non-MS inflammatory central nervous system (CNS) disorders. Resolution of CSF proteins on three pH gradients (3-10, 4-7 and 6-11) enabled identification of a total of 430 spots in the MS CSF proteome that represented 61 distinct proteins. The gels containing MS CSF revealed 103 protein spots that were not seen on control gels. All but four of these 103 spots were proteins known to be present in normal human CSF. The four exceptions were: CRTAC-IB (cartilage acidic protein), tetranectin (a plasminogen-binding protein), SPARC-like protein (a calcium binding cell signalling glycoprotein), and autotaxin t (a phosphodiesterase). It remains unknown whether these four proteins are related to the cause and pathogenesis of MS. PMID:15222687
Hammack, B N; Fung, K Y C; Hunsucker, S W; Duncan, M W; Burgoon, M P; Owens, G P; Gilden, D H
Spontaneous cerebrospinalfluid (CSF) leaks from the fallopian canal are extremely rare, as only a few cases have been reported in the world literature. We describe a case of spontaneous CSF otorrhea through an enlarged geniculate fallopian canal. The patient was a 45-year-old woman who presented with a history of CSF rhinorrhea and otorrhea from the right ear. Myringotomy and tube insertion revealed CSF otorrhea. Contrast-enhanced computed tomography revealed that the geniculate fossa was smoothly enlarged (demonstrating remodeling of bone). A middle fossa craniotomy with temporal bone exploration was performed. Intraoperative inspection detected the presence of a fistula secondary to a lateral extension of the subarachnoid space through the labyrinthine segments of the fallopian canal. We discuss the management of this unusual finding, which involves sealing the fistula while preserving facial nerve function. PMID:23532657
Herbowski (2013) suggested recently the Egyptian Imhotep from the 3rd dynasty in Egypt to be the discoverer of cerebrospinalfluid. There are, however, no sources within the first 2000 years after Imhotep suggesting him to be in any way connected with the field of medicine. Over the course of three millennia Imhotep evolves into the sage who besides architecture also masters the arts of medicine, magic, astronomy, and astrology, at the same time as him being transformed from man to demi-God, and finally to a God. The identification of Imhotep as a doctor has thus little to do with facts and it is unlikely that he had anything to do with the Edwin-Smith papyrus from a much later period where CSF is first mentioned. PMID:24744920
beta-endorphin is a brain peptide with potent morphine-like activity structurally related to the anterior pituitary hormone beta-lipotrophin (beta-L.P.H.). We have developed a radioimmunoassay for human beta-endorphin in plasma and cerebrospinalfluid (C.S.F.). Since the antiserum also reacts with beta-L.P.H., beta-endorphin was distinguished by using a second antiserum which measures beta-L.P.H. alone. With these two immunoassay systems and gel chromatography, we found beta-endorphin in all 20 C.S.F. samples tested at a concentration always higher than, but with no other relationship to, that in plasma. beta-endorphin was found in C.S.F. of patients who had hypopituitarism and undetectable plasma-beta-endorphin, suggesting that it is synthesized in the brain rather in the pituitary. PMID:78323
Jeffcoate, W J; Rees, L H; McLoughlin, L; Ratter, S J; Hope, J; Lowry, P J; Besser, G M
Cladosporium cladosporioides was isolated from three subsequent cerebrospinalfluid specimens and from a brain biopsy specimen of a human patient. Susceptibility testing of the isolate was performed against seven antifungal agents. PMID:12472729
This article celebrates the re-launch of CerebrospinalFluid Research in its new format as Fluids and Barriers of the CNS. Editors-in Chief, Hazel Jones and Tetsuya Terasaki, anticipate that this expanded journal will provide a unique and specialist platform for the publication of research in cerebrospinalfluid and all brain barriers and fluid systems in both health and disease.
Human cerebrospinalfluid has been found to mimic the effect of ouabain on net Na+ efflux and 86Rb+ influx across erythrocyte membranes and on the in vitro activity of a purified Na+/K+-ATPase (ATP phosphohydrolase, EC 184.108.40.206) derived from canine kidney. These results indicate the possible existence in human cerebrospinalfluid of an endogenous factor with ouabain-like activity, which might be linked to sodium metabolism.
Cerebrospinalfluid (CSF) penetration and the pharmacokinetics of vancomycin were studied after contin- uous infusion (50 to 60 mg\\/kg of body weight\\/day after a loading dose of 15 mg\\/kg) in 13 mechanically ventilated patients hospitalized in an intensive care unit. Seven patients were treated for a sensitive bacterial meningitis and the other six patients, who had a severe concomitant neurologic
JACQUES ALBANESE; MARC LEONE; BERNARD BRUGUEROLLE; MARIE-LAURE AYEM; BRUNO LACARELLE; CLAUDE MARTIN
Eighty-four cerebrospinalfluid (CSF) samples from different children who presented with signs and symp- toms of meningitis were evaluated for the presence of Mycobacterium tuberculosis complex organisms by the Gen- Probe Amplified Mycobacterium tuberculosis Direct Test (MTD; Gen-Probe, San Diego, Calif.). All CSF samples had negative acid-fast smears by the Ziehl-Neelsen staining method. M. tuberculosis was recovered from five samples.
ANNE M. LANG; JESUS FERIS-IGLESIAS; CHABELA PENA; JACQUELINE F. SANCHEZ; LESLIE STOCKMAN; PAUL RYS; GLENN D. ROBERTS; NANCY K. HENRY; DAVID H. PERSING; FRANKLIN R. COCKERILL; Robert Reid
Cerebrospinalfluid (CSF) and blood were obtained at the time of myelographic examinations from 40 adult, male, human subjects with no neurologic or metabolic abnormalities. Vitamin E (tocopherols) concentrations were determined by liquid chromatography. In subjects with normal concentrations of CSF protein (n = 22), the alpha- and gamma-tocopherol concentrations were 29.2 +/- 9.5 (mean +/- SD) and 6.5 +/- 3.6 nmol/L, respectively, in CSF and 26.0 +/- 8.1 and 6.0 +/- 3.6 mumol/L, respectively, in serum. The concentrations of alpha-tocopherol in CSF correlated significantly (P less than 0.001) with both total protein and albumin concentrations, suggesting that tocopherol transport into CSF is linked with that of plasma proteins. In vitro oxidation of vitamin E in CSF by the free-radical generator 2,2'-azobis-(2-amidinopropane) hydrochloride showed a measurable induction (lag) period. This is due to the presence of other antioxidants in human CSF. PMID:1984352
Vatassery, G T; Nelson, M J; Maletta, G J; Kuskowski, M A
The epithelial cells of the choroid plexuses secrete cerebrospinalfluid (CSF), by a process which involves the transport of Na+, Cl- and HCO3- from the blood to the ventricles of the brain. The unidirectional transport of ions is achieved due to the polarity of the epithelium, i.e. the ion transport proteins in the blood-facing (basolateral) membrane are different to those in the ventricular (apical) membrane. The movement of ions creates an osmotic gradient which drives the secretion of H2 O. A variety of methods (e.g. isotope flux studies, electrophysiological, RT-PCR, in situ hybridization and immunocytochemistry) have been used to determine the expression of ion transporters and channels in the choroid plexus epithelium. Most of these transporters have now been localized to specific membranes. For example, Na+-K+ ATPase, K+ channels and Na+-2Cl--K+ cotransporters are expressed in the apical membrane. By contrast the basolateral membrane contains Cl--HCO3 exchangers, a variety of Na+ coupled HCO3- transporters and K+-Cl- cotransporters. Aquaporin 1 mediates water transport at the apical membrane, but the route across the basolateral membrane is unknown. A model of CSF secretion by the mammalian choroid plexus is proposed which accommodates these proteins. The model also explains the mechanisms by which K+ is transported from the CSF to the blood.
BROWN, P. D.; DAVIES, S. L.; SPEAKE, T.; MILLAR, I. D.
Objectives To share our experience of cerebrospinalfluid (CSF) gusher in cochlear implantation. Methods Demographic, radiological, and surgical results of patients with CSF gusher in 523 consecutive cochlear implant recipients including children and adults as well as our management technique were evaluated and a review of the literature has been included. Results Fifteen (2.87%) cases had CSF gusher. Two patients (13.3%) were adults with post-lingual hearing loss and the rest 12 (86.7%) were children with congenital hearing loss. Twelve patients (80%) had various types of inner ear malformation. Three patients (20%) had no predictable risk of CSF gusher from history or pre-operative imaging. In all patients, CSF gushers were controlled with our technique of packing the electrode entrance site with no additional measures. Conclusion CSF gusher may occur with post-lingual hearing loss and in children with apparently unremarkable imaging and history. Thus, surgeons should always be ready to manage it. Management of CSF gusher can be mainly performed during the initial surgery by precise tight packing of the electrode entrance site. Furthermore, non-surgical or surgical measures are rarely required to stop a persistent leak. Our results show that our management technique may be recommended as well. PMID:24660749
Cerebral amyloid angiopathy is caused by deposition of the amyloid ? protein in the cerebral vasculature. In analogy to previous observations in Alzheimer disease, we hypothesized that analysis of amyloid ?40 and ?42 proteins in the cerebrospinalfluid might serve as a molecular biomarker. We observed strongly decreased cerebrospinalfluid amyloid ?40 (p < 0.01 vs controls or Alzheimer disease) and amyloid ?42 concentrations (p < 0.001 vs controls and p < 0.05 vs Alzheimer disease) in cerebral amyloid angiopathy patients. The combination of amyloid ?42 and total tau discriminated cerebral amyloid angiopathy from controls, with an area under the receiver operator curve of 0.98. Our data are consistent with neuropathological evidence that amyloid ?40 as well as amyloid ?42 protein are selectively trapped in the cerebral vasculature from interstitial fluid drainage pathways that otherwise transport amyloid ? proteins toward the cerebrospinalfluid.
Verbeek, Marcel M.; Kremer, Berry P. H.; Rikkert, Marcel Olde; van Domburg, Peter H. M. F.; Skehan, Maureen E.; Greenberg, Steven M.
Accurate enumeration of cells in the cerebrospinalfluid is not feasible with the current method of counting cells in the Fuchs Rosenthal or Neubauer chamber when the count is near normal since the volume of fluid examined is too small. A sample of adequate volume to permit such accurate assessment may be collected from the lumbar puncture needle into a syringe through a ruled membrane filter in a Swinney cartridge. A study of 291 samples shows that the upper limit of the normal cerebrospinalfluid count is 2000 cells/ml (2/cmm) and not 5000/ml (5/cmm) as is currently accepted. Images
Oligoclonal bands in cerebrospinalfluid reflect local B-cell responses associated with various neuroinflammatory disorders. In opsoclonus-myoclonus syndrome, cerebrospinalfluid B-cell expansion was demonstrated, but no studies of oligoclonal bands are available. In a prospective case-control study of 132 children (103 with opsoclonus-myoclonus, 29 neurologic control subjects), cerebrospinalfluid oligoclonal bands, measured by isoelectric focusing with immunofixation, were observed in 35% with opsoclonus-myoclonus and none of the control subjects, with the highest frequency in severe cases (56%). In oligoclonal band-positive patients, the mean band number was 5 ± 3 S.D. (range, 2-10) and the total severity score was significantly higher than in band-negative patients, whereas the frequency of CD19(+) B cells, opsoclonus-myoclonus duration, neuroblastoma detection, and relapse history did not differ. The cerebrospinalfluid immunoglobulin G synthesis rate, immunoglobulin index, and Q albumin were normal. In 17 untreated children receiving adrenocorticotropic hormone, intravenous immunoglobulins, and rituximab, the number of oligoclonal band-positive decreased by 75%, and the mean band count fell by 80%. Oligoclonal band detection adds useful information to neuroimmunologic "staging" in opsoclonus-myoclonus. However, flow cytometry provides a more sensitive measure of B-cell infiltration. Cerebrospinalfluid oligoclonal bands warrant monitoring in long-term follow-up studies of disease-modifying drugs for opsoclonus-myoclonus. PMID:21723456
Pranzatelli, Michael R; Slev, Patricia R; Tate, Elizabeth D; Travelstead, Anna L; Colliver, Jerry A; Joseph, Suja Anne
We report a patient with primary leptomeningeal melanocytosis presenting as chronic meningitis. A previously healthy 27-year-old man presented with 2 months of severe headaches and photophobia. A lumbar puncture was notable for a highly elevated cerebrospinalfluid (CSF) protein level without pleocytosis. Imaging at the time of admission suggested only meningitis without the presence of parenchymal lesions. On the basis of the CSF findings, early meningeal biopsy was performed, leading to the diagnosis of a meningeal melanocytic neoplasm. Early meningeal biopsy should be considered in patients with meningitis when the CSF profile suggests the possibility of a central nervous system neoplasm. PMID:24355206
Honigberg, Michael C; Papavassiliou, Efstathios; Cohen, Yehuda Z
Transferrin in cerebrospinalfluid (CSF) exists as a mixture of silao and asialo glycoforms believed to originate from liver and brain respectively. We have previously shown that alteration in the asialo glycoform pattern could be an indication of certain anomalies in the central nervous system. Additionally, CSF asialo-transferrin has been shown to be a reliable marker to assess cerebrospinal leakage in head trauma. Therefore, the CSF transferrin glycoform pattern could be a useful diagnostic and prognostic tool. In this study we sought to characterize, in-depth, the transferrin glycovariants in cerebrospinalfluid using a combination of two-dimensional gel electrophoresis and high precision mass spectrometry analysis. Cerebrospinalfluid transferrin was detected as multiple spots (seven major spots) with different isoelectric points and slight shift in apparent molecular mass. High resolution (>60,000) and high accuracy (< 3 ppm error) mass spectrometry analysis revealed that each spot had a unique glycopeptide signature. MSn analysis enabled characterization of the glycan structure directly from the in-gel digested spots. The multiple spots detected for cerebrospinalfluid transferrin were mainly due to heterogeneity of di-antennary and tri-antennary glycans harboring a varying number of terminal N-acetylneuraminic acids and the existence of a high mannose and high N-acetylhexosamine glycosylated species.
Transferrin in cerebrospinalfluid (CSF) exists as a mixture of silao and asialo glycoforms believed to originate from liver and brain respectively. We have previously shown that alteration in the asialo glycoform pattern could be an indication of certain anomalies in the central nervous system. Additionally, CSF asialo-transferrin has been shown to be a reliable marker to assess cerebrospinal leakage in head trauma. Therefore, the CSF transferrin glycoform pattern could be a useful diagnostic and prognostic tool. In this study we sought to characterize, in-depth, the transferrin glycovariants in cerebrospinalfluid using a combination of two-dimensional gel electrophoresis and high precision mass spectrometry analysis. Cerebrospinalfluid transferrin was detected as multiple spots (seven major spots) with different isoelectric points and slight shift in apparent molecular mass. High resolution (>60,000) and high accuracy (< 3 ppm error) mass spectrometry analysis revealed that each spot had a unique glycopeptide signature. MS(n) analysis enabled characterization of the glycan structure directly from the in-gel digested spots. The multiple spots detected for cerebrospinalfluid transferrin were mainly due to heterogeneity of di-antennary and tri-antennary glycans harboring a varying number of terminal N-acetylneuraminic acids and the existence of a high mannose and high N-acetylhexosamine glycosylated species. PMID:22408387
Background Cerebrospinalfluid (CSF) findings are often used to diagnose meningitis in neonates given antibiotics before the lumbar puncture is performed. Traumatic lumbar punctures are common and complicate interpretation of CSF white blood cell counts. The purpose of this study is to evaluate the diagnostic utility of adjusting CSF white blood cell counts based on CSF and peripheral red blood cell counts. Methods Cohort study of lumbar punctures performed between 1997 and 2004 at 150 neonatal intensive care units managed by the Pediatrix Medical group. Traumatic lumbar punctures were defined as CSF specimens with ?500 red blood cells/mm3. CSF white blood cell counts were adjusted downward for traumatic lumbar punctures using several commonly used methods. We calculated sensitivity, specificity, likelihood ratios, and area under the receiver operating characteristic curve of unadjusted and adjusted CSF white blood cell counts for predicting meningitis in neonates with traumatic lumbar punctures. Results Of 6,374 lumbar punctures, 2,519 (39.5%) were traumatic. 114/6,374 (1.8%) were positive for meningitis; 50 neonates with traumatic lumbar punctures had meningitis. The areas under the receiver operating characteristic curve for white blood cell count unadjusted and adjusted by all methods were similar. Conclusions Adjustment of CSF white blood cell counts to account for increased red cells does not improve diagnostic utility. Adjustment can result in loss of sensitivity with marginal gain in specificity. Adjustment of WBC counts in the setting of a traumatic lumbar puncture does not aid in the diagnosis of bacterial and fungal meningitis in neonates.
Greenberg, Rachel G.; Smith, P. Brian; Cotton, C. Michael; Moody, M. Anthony; Clark, Reese H.; Benjamin, Daniel K.
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A modified latex agglutination test was designed and evaluated for the rapid detection of Streptococcus pneumoniae and haemophilus influenzae type b capsular antigens, and for direct serotyping of Streptococcus pneumoniae in the cerebrospinalfluid. Reagents were prepared by sensitizing latex particles with Omniserum (against 83 capsular serotypes of pneumococci) and Haemophilus influenzae type b burro antiserum. For serotyping reagents, latex particles were similarly coated with nine pneumococcal pool (a to I) antisera and 46 individual pneumococcal serogroup/serotype specific antisera. The test was performed on cerebrospinalfluid from 298 patients with suspected meningitis. Serotyping was done directly on untreated cerebrospinalfluid samples showing positive reactions with the Omniserum reagent. Pneumococcal or Haemophilus influenzae type b antigens were detected in 41 patients; in 32 of these the etiology was established by culture and in 2 by smear examination. Five of the remaining seven cases were judged clinically and by cytological examination of cerebrospinalfluid to have partially treated bacterial meningitis. In two cases the test was false positive. The overall sensitivity and specificity of the latex agglutination test for the detection of Streptococcus pneumoniae and Haemophilus influenzae type b antigens was 100% and 96.8% respectively. The commonest pneumococcal serotypes were type 1 (30%), types 6 and 19 (10% each). The latex agglutination test is rapid and simple to perform, yielding serotype data directly by testing of cerebrospinalfluid. PMID:8839641
Singhal, A; Lalitha, M K; John, T J; Thomas, K; Raghupathy, P; Jacob, S; Steinhoff, M C
Summary Aim of this report is to describe the long-term results of endoscopic endonasal repair of cerebrospinalfluid leak using a septal mucoperichondrial graft. A case series of 52 patients operated for cerebrospinalfluid rhinorrhea between 1990 and 2006 is presented. All patients underwent surgical treatment for endoscopic endonasal closure of a cerebrospinalfluid leak using a septal mucoperichondrial graft. No lumbar drain and fluorescein tests were used. The intra-operative localization of the fistula was aided by Valsalva’s manoeuvre by the anaesthetist. The success rate, after the first attempt, was 88.5% (46/52 patients); for the remaining 11.5% (6/52 patients), a second attempt was necessary which proved successful in 5 cases, raising the overall success rate to 98.1% (51/52 patients). Relapse occurred in only one case (1.9%), after the second attempt. In conclusion, a free mucoperichondrial graft offered good results for cerebrospinalfluid leak repair. In the Authors’ experience, a high success rate can be achieved without the use of intrathecal fluorescein and lumbar drain.
Presutti, L; Mattioli, F; Villari, D; Marchioni, D; Alicandri-Ciufelli, M
Relapsing Devic’s neuromyelitis optica (DNO) may be clinically undistinguishable from multiple sclerosis (MS), thus the differential diagnosis relies mainly on neuroimaging and cerebrospinalfluid (CSF) findings. We studied CSF samples from 44 patients with DNO submitted to at least one lumbar puncture. Pleocytosis, IgG synthesis and blood brain barrier damage were the most frequent abnormalities, pleocytosis being very suggestive of
Linezolid is a new antimicrobial agent effective against drug-resistant gram-positive pathogens commonly responsible for central nervous system (CNS) infections in neurosurgical patients hospitalized in intensive care units. In order to study the penetration of this antimicrobial into the cerebrospinalfluid (CSF) of such patients, the disposition of linezolid in serum and CSF was studied in 14 neurosurgical patients given linezolid
Pavlos Myrianthefs; Sophia L. Markantonis; Konstantinos Vlachos; Maria Anagnostaki; Eleni Boutzouka; Dimitris Panidis; Georgios Baltopoulos
It has been suggested that nitric oxide (NO) could be implicated in the pathogenesis of multiple sclerosis (MS). Recently, two groups reported increased cerebrospinalfluid (CSF) nitrate levels (oxidation product that provides an indirect estimation of NO) in MS patients. However, another group did not confirm these findings. We studied the CSF and plasma levels of nitrate with a kinetic
Fernando de Bustos; José Antonio Navarro; Clara de Andrés; José Antonio Molina; Félix Javier Jiménez-Jiménez; Miguel Ortí-Pareja; Teresa Gasalla; Antonio Tallón-Barranco; Antonio Martínez-Salio; Joaquín Arenas
14 cases of post-traumatic cerebrospinalfluid leaks, sealed with tissue adhesives and fascia, or galea, are reported. None of the patients had recurrence in a follow-up ranging from five months to three years. Tissue adhesives provided a tough adhesion of the patch and, as a consequence, an immediate and stable repair of the leak. PMID:1223246
A 38-year-old patient developed meningitis after a complicated kidney transplantation and organ rejection. Ureaplasma urealyticum was identified as the etiological agent by molecular and microbiological analyses of the cerebrospinalfluid. The patient was successfully treated with doxycycline and chloramphenicol. This is the first report of Ureaplasma urealyticum meningitis in an adult.
Bacteroides fragilis is an obligate anaerobic bacillus residing in the normal intestinal flora of the colon. Anaerobic bacterial meningitis due to this pathogen is rarely diagnosed and if present, a predisposing source of infection should be actively sought for. Anaerobic cultures of cerebrospinalfluids should be done for patients with meningitis, especially those with concomitant pathologies that predispose to anaerobic infections. Two cases of anaerobic meningitis due to Bacteroides fragilis, one associated with cholesteotoma and the other with nasopharyngeal carcinoma, are reported. Both were successfully treated with metronidazole. PMID:7997905
Background Arachnoid cyst (AC) fluid has not previously been compared with cerebrospinalfluid (CSF) from the same patient. ACs are commonly referred to as containing "CSF-like fluid". The objective of this study was to characterize AC fluid by clinical chemistry and to compare AC fluid to CSF drawn from the same patient. Such comparative analysis can shed further light on the mechanisms for filling and sustaining of ACs. Methods Cyst fluid from 15 adult patients with unilateral temporal AC (9 female, 6 male, age 22-77y) was compared with CSF from the same patients by clinical chemical analysis. Results AC fluid and CSF had the same osmolarity. There were no significant differences in the concentrations of sodium, potassium, chloride, calcium, magnesium or glucose. We found significant elevated concentration of phosphate in AC fluid (0.39 versus 0.35 mmol/L in CSF; p = 0.02), and significantly reduced concentrations of total protein (0.30 versus 0.41 g/L; p = 0.004), of ferritin (7.8 versus 25.5 ug/L; p = 0.001) and of lactate dehydrogenase (17.9 versus 35.6 U/L; p = 0.002) in AC fluid relative to CSF. Conclusions AC fluid is not identical to CSF. The differential composition of AC fluid relative to CSF supports secretion or active transport as the mechanism underlying cyst filling. Oncotic pressure gradients or slit-valves as mechanisms for generating fluid in temporal ACs are not supported by these results.
A 61-year-old man developed disturbance of consciousness for 2 weeks. He showed neck stiffness and hyporeflexia. Analysis of his cerebrospinalfluid (CSF) revealed pleocytosis and markedly reduced glucose contents. Adenosine deaminase (ADA) levels in the CSF were elevated (28.8 IU/l). Brain magnetic resonance imagings showed enhancement of the leptomeninges. Tuberculous meningitis was considered, but antituberculous drug was not effective. Repeated cytological analysis of the CSF demonstrated atypical cells with enlarged unevenly distributed nuclei and immunoreactive with glial fibrillary acidic protein. We diagnosed him as leptomeningeal gliomatosis. CSF ADA may be elevated in this rare disorder, and here we emphasize that repeated cytological analysis with immunohistochemical staining was useful for diagnosis. PMID:24807273
Postoperative cerebrospinalfluid (CSF) rhinorrhea after septoplasty is a known entity resulting from errors in surgical technique and improper handling of the perpendicular plate of the ethmoid bone. When these occur, urgent management is necessary to prevent deleterious sequelae such as meningitis, intracranial abscess, and pneumocephalus. Encephaloceles are rare occurrences characterized by herniation of intracranial contents through a skull base defect that can predispose patients to CSF rhinorrhea. In this report, we present a case of CSF rhinorrhea occurring 2 weeks after septoplasty likely from manipulation of an occult anterior skull base encephalocele. To our knowledge, no previous similar case has been reported in the literature. Otolaryngologists should be aware of the possibility of occult encephaloceles while performing septoplasties because minimal manipulation of these entities may potentially result in postoperative CSF leakage.
Soni, Resha S.; Choudhry, Osamah J.; Liu, James K.
The objective of this prospective study was to examine the effect of fluid restriction on body water and the outcome of children with acute meningitis. Fifty consecutively hospitalized children with acute meningitis, divided into two groups (A, without hyponatremia; and B, with hyponatremia), were randomly assigned to receive either normal maintenance (M) or restricted (R subgroup) (65 to 70% of M subgroup) fluids during the first 48 hours. Total body water, extracellular water (ECW), serum and urinary sodium and plasma and urinary osmolality were measured at admission and after 48 hours. In both groups children receiving restricted fluids showed a significant decrease in the mean total body water and ECW whereas body water remained unchanged in those on maintenance fluids. Children having an ECW reduction of 10 ml/kg or more in 48 hours had a significantly lower intact survival (10 of 28, 36%) than those with < 10 ml/kg or no reduction of ECW (15 of 22, 64%) (P < 0.05). The mortality was also higher in the former (7 of 28, 25%) than in the latter (2 of 22, 9%). On multiple stepwise regression analysis, ECW volume at admission (partial r2 0.20), ECW loss in 48 hours (partial r2 0.13) and plasma osmolality at admission (partial r2 0.22) were significantly related to outcome. We conclude that fluid restriction does not improve the outcome of acute meningitis. Indeed a decrease in ECW volume at 48 hours increases the likelihood of adverse outcome. PMID:7667054
Singhi, S C; Singhi, P D; Srinivas, B; Narakesri, H P; Ganguli, N K; Sialy, R; Walia, B N
Chronic meningitis is defined as the persistence of clinical symptoms and signs of meningitis, with or without abnormal cerebrospinalfluid, for more than four weeks. In as many as one third of cases, no cause is found. In the remainder, infective, neoplastic and so-called aseptic disorders may be identified. Important infective causes include partially treated bacterial (pyogenic), tuberculous, syphilitic, Lyme and fungal meningitis. Sarcoidosis, Behçet's disease, vasculitis and drugs are major non-infective, non-malignant causes. The definitive diagnosis of the cause of chronic meningitis may be made only after extensive investigation. This review describes the clinical features and causes of chronic and recurrent meningitis, and provides an algorithm for investigation and treatment. PMID:19015295
Brinker et al. extensively reviewed recent findings about CSF circulation in a recent article: “A new look at cerebrospinal circulation”, but did not analyze some important available data in sufficient detail. For example, our findings as well as some clinical data and experimental results obtained from different animal species, do not support unidirectional CSF circulation but strongly suggest that there are cardiac cycle-dependent systolic-diastolic to-and-fro cranio-spinal CSF movements. These are based on: a) physiological oscillations of arterial and venous blood during cranio-spinal blood circulation; b) respiratory activity, and c) body activity and posture. That kind of complex CSF movement could explain the observed distribution of many different substances in all directions along the CSF system and within central nervous system tissue. It seems that efflux transport systems at capillary endothelium may be more important for brain homeostasis than the removal of metabolites by CSF flow. Thus, when discussing the CSF dynamics we suggest that a more appropriate term would be CSF movement rather than CSF circulation.
Dementia due to Alzheimer’s disease (AD) is estimated to reach epidemic proportions by the year 2030. Given the limited accuracy of current AD clinical diagnosis, biomarkers of AD pathologies are currently being sought. Reductions in cerebrospinalfluid levels of ?-amyloid 42 (a marker of amyloid plaques) and elevations in tau species (markers of neurofibrillary tangles and/or neurodegeneration) are well-established as biomarkers useful for AD diagnosis and prognosis. However, novel markers for other features of AD pathophysiology (e.g., ?-amyloid processing, neuroinflammation and neuronal stress/dysfunction) and for other non-AD dementias are required to improve the accuracy of AD disease diagnosis, prognosis, staging and therapeutic monitoring (theragnosis). This article discusses the potential of several promising novel cerebrospinalfluid analytes, highlights the next steps critical for advancement in the field, and provides a prediction on how the field may evolve in 5–10 years.
The caudate nucleus has the highest acetylcholinesterase (AChE) activity in the brain and it has been shown that autopsied brain tissue of patients with Huntington's disease (HD) have reduced levels of acetylcholine. Because of these findings, the cholinergic function in HD was studied by measuring cerebrospinalfluid (CSF) choline levels and AChE activity during a randomized, double-blind, cross-over, placebo-controlled clinical
A micro-scale method for separation and measurement of dityrosine in human cerebrospinalfluid (CSF) is described utilizing liquid-liquid extraction and ion-paired, reversed-phase high-performance liquid chromatography with fluorimetric detection. A mobile phase containing 1-heptanesulfonic acid linearly increased in methanol from 0 to 100% over 30 min allows the resolution of dityrosine from other fluorescent compounds with excitation at 285 nm and
Maged Abdelrahim; Elena Morris; Jeannean Carver; Stephen Facchina; Alison White; Ajay Verma
Succinyladenosine (S-Ado) is a biochemical marker of adenylosuccinase deficiency – the genetic defect of purine de novo synthesis. S-Ado has been previously reported as normally undetectable in cerebrospinalfluid (CSF) of children not suffering from this defect. In present study, we employed solid-phase extraction and thin-layer chromatography for isolation of a compound with spectral and chromatographic characteristics identical to S-Ado
Jakub Krijt; Stanislav Kmoch; Hana Hartmannová; Vladim??r Havl???ek; Ivan Šebesta
In neurodegenerative diseases, cerebrospinalfluid analysis (CSF) is predominantly performed to exclude inflammatory diseases\\u000a and to perform a risk assessment in dementive disorders by measurement of tau proteins and amyloid beta peptides. However,\\u000a large scale data on basic findings of CSF routine parameters are generally lacking. The objective of the study was to define\\u000a a normal reference spectrum of routine
Sarah Jesse; Johannes Brettschneider; Sigurd D. Süssmuth; Bernhard G. Landwehrmeyer; Christine A. F. von Arnim; Albert C. Ludolph; Hayrettin Tumani; Markus Otto
We describe a convenient method for the separation and quantification of xanthine, hypoxanthine, and uric acid in 20 .tL of cerebrospinalfluid (CSF) with use of HPLC and ultraviolet detection. The analysis is performed on a Sepha- ron SGX C18 column and the elution system consists of potassium phosphate buffer, pH 5.1, with 20 mL\\/L metha- nol. The lower limit
The goal of this study was to design a reliable method to quantify and visualize the anatomical distribution of cerebrospinalfluid (CSF) intracranially. The method should be clinically applicable and based on multispectral analysis of three-dimensional (3D) magnetic resonance images. T1-weighted, T2-weighted and proton density-weighted fast 3D gradient pulse sequences were used to form high resolution multispectral 3D images of
Arvid Lundervold; Torfinn Taxt; Lars Ersland; Anne Marie Fenstad
The timing and regional specificity of cerebrospinalfluid (CSF) enlargements have not been well described in schizophrenia. High-resolution magnetic resonance images and computational image analysis methods were used to localize cross-sectional changes in lateral ventricle and sulcal and subarachnoid CSF in first episode schizophrenia patients (51 males\\/21 females) and healthy subjects (37 males\\/41 females). Volumes were obtained for each lateral
Katherine L. Narr; Robert M. Bilder; Roger P. Woods; Paul M. Thompson; Philip Szeszko; Delbert Robinson; Martina Ballmaier; Bradley Messenger; YungPing Wang; Arthur W. Toga
A competitive enzyme-linked immunosorbent assay with high sensitivity has been developed for measuring ubiquitin reactivity of paired helical filaments (PHF). Using the assay, ubiquitin immunoreactivity was estimated in the cerebrospinalfluid (CSF) of 44 patients who had been clinically diagnosed as having Alzheimer's disease (AD) and of 38 control patients, including 20 neurological cases. Monoclonal antibody (mAb) 5–25 to isolated
G. P. Wang; K. Iqbal; G. Bucht; B. Winblad; H. M. Wisniewski; I. Grundke-Iqbal
Methicillin-resistant Staphylococcus epidermidis (MRSE) can cause nosocomial meningitis in the presence of prosthetic devices. Vancomycin is the treatment of choice, but its penetration into the cerebrospinalfluid is poor, especially in cases without severe meningeal inflammation. We successfully used linezolid to treat a case of posttraumatic MRSE meningitis with a low-level inflammatory response. Therapeutic effectiveness was documented microbiologically and by
Wolfgang A. Krueger; Bernd Kottler; Bernd E. Will; Alexandra Heininger; Heinz Guggenberger; Klaus E. Unertl
There is evidence that the treatment of bacterial meningitis with antibiotics liberates harmful bacterial pro- ducts in the subarachnoid space (SAS). This enhances meningeal inflammation and in particular the recruit- ment of leukocytes into the cerebrospinalfluid (CSF), which has been shown to be more harmful than bene- ficial in this disease. In this study, we used a rabbit meningitis
Coenurosis, a neurological parasitic infection of ruminants caused by the larval stage of Taenia multiceps, is commonly reported in Sardinia, the most representative region for ovine population in Italy. Chronic form appears as a consequence of cyst development, frequently reported in the brain and spinal cord. Diagnostic suspect of coenurosis is based on physical and neurological examination. The aim of this article is to describe physical, biochemical and cytological aspects of cisternal cerebrospinalfluid of 24 sheep with chronic coenurosis and to evaluate whether these alterations are helpful in the diagnosis of coenurosis. Cerebrospinalfluid was altered in 20 animals (83.3%). Increase of total protein was revealed in 7 animals (29.2%); an increase of total nucleated cell count was observed in 18 samples (75%). Cytological examination revealed mononuclear pleocytosis in 17 animals (70.1%). Eosinophils were observed in 16 animals in various degree (66.7%). Our results show that cerebrospinalfluid confirms signs of Central Nervous System inflammation in 20 animals out of 24 (83.3%) and in particular it was useful to identify a parasitic inflammation in 66.7% of the animals in which eosinophils were observed. Considering the results of this study, the very absence of significant neutrophilic pleocytosis could be considered useful to diagnose chronic cerebral coenurosis. PMID:24715594
Zobba, Rosanna; Manunta, Maria Lucia; Evangelisti, Maria Antonietta; Alberti, Alberto; Visco, Stefanoa; Dimauro, Corrado; Pinna Parpaglia, Maria Luisa
Cerebrospinalfluid is routinely collected for the diagnosis and monitoring of patients with neurological malignancies. However, little is known as to how its constituents may change in a patient when presented with a malignant glioma. Here, we used a targeted mass-spectrometry based metabolomics platform using selected reaction monitoring with positive/negative switching and profiled the relative levels of over 124 polar metabolites present in patient cerebrospinalfluid. We analyzed the metabolic profiles from 10 patients presenting malignant gliomas and seven control patients that did not present malignancy to test whether a small sample size could provide statistically significant signatures. We carried out multiple unbiased forms of classification using a series of unsupervised techniques and identified metabolic signatures that distinguish malignant glioma patients from the control patients. One subtype identified contained metabolites enriched in citric acid cycle components. Newly diagnosed patients segregated into a different subtype and exhibited low levels of metabolites involved in tryptophan metabolism, which may indicate the absence of an inflammatory signature. Together our results provide the first global assessment of the polar metabolic composition in cerebrospinalfluid that accompanies malignancy, and demonstrate that data obtained from high throughput mass spectrometry technology may have suitable predictive capabilities for the identification of biomarkers and classification of neurological diseases.
Locasale, Jason W.; Melman, Tamar; Song, Susan; Yang, Xuemei; Swanson, Kenneth D.; Cantley, Lewis C.; Wong, Eric T.; Asara, John M.
Cerebrospinalfluid (CSF) biomarkers, including soluble amyloid ?-42 (A?-42) and phosphorylated-tau (P-tau), reflect core pathophysiological features of Alzheimer's disease (AD). AD is frequently a concomitant pathology in older patients with idiopathic normal-pressure hydrocephalus (iNPH), and somewhat similar altered CSF dynamics exist in both AD and iNPH. We therefore investigated relationships between lumbar CSF biomarkers A?-42 and P-tau and clinical parameters in iNPH patients, along with differences in these biomarkers between CSF tap test (CSFTT) responders and non-responders. Thirty-one iNPH patients (14 CSFTT responders and 17 CSFTT non-responders) were included in the final analysis. We found lower CSF A?-42 correlated with poor cognitive performance (r=0.687, p<0.001 for Korean Mini Mental State Examination; r=0.568, p=0.001 for Frontal Assessment Battery; r=-0.439, p=0.014 for iNPH grading scale [iNPHGS] cognitive score; r=-0.588, p=0.001 for Clinical Dementia Rating Scale), and lower CSF P-tau correlated with gait dysfunction (r=-0.624, p<0.001 for Timed Up and Go Test; r=-0.652, p<0.001 for 10meter walking test; r=-0.578, p=0.001 for Gait Status Scale; r=-0.543, p=0.002 for iNPHGS gait score). In subgroup analysis, CSF P-tau/A?-42 ratios were significantly higher in CSFTT non-responders compared to responders (p=0.027). Two conjectures are suggested. One, CSF biomarkers may play different and characteristic roles in relation to different iNPH symptoms such as cognition and gait. Two, comorbid AD pathology in iNPH patients may affect the response to the CSFTT. Larger studies using combinations of other biomarkers associated with AD would be necessary to evaluate these hypotheses. PMID:24836892
Background There is little knowledge concerning the content and the mechanisms of filling of arachnoid cysts. The aim of this study was to compare the protein content of arachnoid cysts and cerebrospinalfluid by quantitative proteomics to increase the understanding of arachnoid cysts. Methods Arachnoid cyst fluid and cerebrospinalfluid from five patients were analyzed by quantitative proteomics in two separate experiments. In a label-free experiment arachnoid cyst fluid and cerebrospinalfluid samples from individual patients were trypsin digested and analyzed by Orbitrap mass spectrometry in a label-free manner followed by data analysis using the Progenesis software. In the second proteomics experiment, a patient sample pooling strategy was followed by MARS-14 immunodepletion of high abundant proteins, trypsin digestion, iTRAQ labelling, and peptide separation by mix-phase chromatography followed by Orbitrap mass spectrometry analysis. The results from these analyzes were compared to previously published mRNA microarray data obtained from arachnoid membranes. Results We quantified 348 proteins by the label-free individual patient approach and 1425 proteins in the iTRAQ experiment using a pool from five patients of arachnoid cyst fluid and cerebrospinalfluid. This is by far the largest number of arachnoid cyst fluid proteins ever identified, and the first large-scale quantitative comparison between the protein content of arachnoid cyst fluid and cerebrospinalfluid from the same patients at the same time. Consistently in both experiment, we found 22 proteins with significantly increased abundance in arachnoid cysts compared to cerebrospinalfluid and 24 proteins with significantly decreased abundance. We did not observe any molecular weight gradient over the arachnoid cyst membrane. Of the 46 proteins we identified as differentially abundant in our study, 45 were also detected from the mRNA expression level study. None of them were previously reported as differentially expressed. We did not quantify any of the proteins corresponding to gene products from the ten genes previously reported as differentially abundant between arachnoid cysts and control arachnoid membranes. Conclusions From our experiments, the protein content of arachnoid cyst fluid and cerebrospinalfluid appears to be similar. There were, however, proteins that were significantly differentially abundant between arachnoid cyst fluid and cerebrospinalfluid. This could reflect the possibility that these proteins are affected by the filling mechanism of arachnoid cysts or are shed from the membranes into arachnoid cyst fluid. Our results do not support the proposed filling mechanisms of oncotic pressure or valves.
... reviewed: 01/30/2011 5 eningitis. Although large epidemics of meningitis do not typically occur in the United States, some countries experience large epidemics. An epidemic is when the disease spreads significantly ...
In 1900, Ernst Overton found that the entry of anilin dyes through the cell membranes of living cells depended on the lipophilicity of the dyes. The brain is surrounded by barriers consisting of lipid layers that possess several inward and outward active transport systems. In the absence of meningeal inflammation, the cerebrospinalfluid (CSF) penetration of anti-infectives in humans estimated by the ratio of the area under the concentration-time curve (AUC) in CSF (AUC(CSF)) to that in serum (AUC(CSF)/AUC(S)) correlated positively with the lipid-water partition coefficient at pH 7.0 (log D) (Spearman's rank correlation coefficient r(S) = 0.40; P = 0.01) and negatively with the molecular mass (MM) (r(S) = -0.33; P = 0.04). The ratio of AUC(CSF) to the AUC of the fraction in serum that was not bound (AUC(CSF)/AUC(S,free)) strongly correlated with log D (r(S) = 0.67; P < 0.0001). In the presence of meningeal inflammation, AUC(CSF)/AUC(S) also correlated positively with log D (r(S) = 0.46; P = 0.002) and negatively with the MM (r(S) = -0.37; P = 0.01). The correlation of AUC(CSF)/AUC(S,free) with log D (r(S) = 0.66; P < 0.0001) was as strong as in the absence of meningeal inflammation. Despite these clear correlations, Overton's rule was able to explain only part of the differences in CSF penetration of the individual compounds. The site of CSF withdrawal (lumbar versus ventricular CSF), age of the patients, underlying diseases, active transport, and alterations in the pharmacokinetics by comedications also appeared to strongly influence the CSF penetration of the drugs studied. PMID:22106225
In North America, the widespread use of vaccines targeting Haemophilus influenzae type b and Streptococcus pneumoniae have dramatically altered the epidemiology of bacterial meningitis, while the methodology for culturing cerebrospinalfluid (CSF) specimens has remained largely unchanged. The aims of this study were 2-fold: to document the current epidemiology of bacterial meningitis at a tertiary care medical center and to assess the clinical utility of routinely querying for anaerobes in CSF cultures. To that end, we assessed CSF cultures submitted over a 2-year period. A brucella blood agar (BBA) plate, incubated anaerobically for 5 days, was included in the culture procedure for all CSF specimens during the second year of evaluation. In the pre- and postimplementation years, 2,353 and 2,302 CSF specimens were cultured, with 49 and 99 patients having positive culture results, respectively. The clinical and laboratory data for patients with positive cultures were reviewed. Anaerobic bacteria were isolated in the CSF samples from 33 patients post-BBA compared to two patients pre-BBA (P = 0.01). The anaerobic isolates included Bacteroides thetaiotaomicron (n = 1), Propionibacterium species (n = 15), and Propionibacterium acnes (n = 19) isolates; all of these isolates were recovered on the BBA. Eight of the 35 patients from whom anaerobic organisms were isolated received antimicrobial therapy. Although six of these patients had central nervous system hardware, two patients did not have a history of a neurosurgical procedure and had community-acquired anaerobic bacterial meningitis. This study demonstrates that the simple addition of an anaerobically incubated BBA to the culture of CSF specimens enhances the recovery of clinically significant anaerobic pathogens. PMID:24622102
Pittman, Meredith E; Thomas, Benjamin S; Wallace, Meghan A; Weber, Carol J; Burnham, Carey-Ann D
Background Most test systems for acetylcholinesterase activity (E.C.220.127.116.11.) are using toxic inhibitors (BW284c51 and iso-OMPA) to distinguish the enzyme from butyrylcholinesterase (E.C.18.104.22.168.) which occurs simultaneously in the cerebrospinalfluid. Applying Ellman's colorimetric method, we were looking for a non-toxic inhibitor to restrain butyrylcholinesterase activity. Based on results of previous in vitro studies bupivacaine emerged to be a suitable inhibitor. Results Pharmacokinetic investigations with purified cholinesterases have shown maximum inhibition of butyrylcholinesterase activity and minimal interference with acetylcholinesterase activity at bupivacaine final concentrations between 0.1 and 0.5 mmol/l. Based on detailed analysis of pharmacokinetic data we developed three equations representing enzyme inhibition at bupivacaine concentrations of 0.1, 0.2 and 0.5 mmol/l. These equations allow us to calculate the acetylcholinesterase activity in solutions containing both cholinesterases utilizing the extinction differences measured spectrophotometrically in samples with and without bupivacaine. The accuracy of the bupivacaine-inhibition test could be confirmed by investigations on solutions of both purified cholinesterases and on samples of human cerebrospinalfluid. If butyrylcholinesterase activity has to be assessed simultaneously an independent test using butyrylthiocholine iodide as substrate (final concentration 5 mmol/l) has to be conducted. Conclusions The bupivacaine-inhibition test is a reliable method using spectrophotometrical techniques to measure acetylcholinesterase activity in cerebrospinalfluid. It avoids the use of toxic inhibitors for differentiation of acetylcholinesterase from butyrylcholinesterase in fluids containing both enzymes. Our investigations suggest that bupivacaine concentrations of 0.1, 0.2 or 0.5 mmol/l can be applied with the same effect using 1 mmol/l acetylthiocholine iodide as substrate.
Kluge, Wolfram H; Kluge, Harald H; Bauer, Heike I; Pietsch, Stefan; Anders, Jens; Venbrocks, Rudolf A
Cervical intradural disc herniation (IDH) is a rare condition and only 25 cases of cervical have been reported. We report a 45-year-old male who presented with sudden onset right lower limb weakness after lifting heavy weight. Magnetic resonance imaging of the cervical spine showed C5/6 disc prolapse with intradural extension. The patient underwent C5/6 discectomy through anterior cervical approach. Postoperatively, the patient improved in stiffness but developed cerebrospinalfluid leak and the leak resolved with multiple lumbar punctures. PMID:21743181
Here, we review the cerebrospinalfluid (CSF) candidate markers with regard to their clinical relevance as potential surrogates for disease activity, prognosis assessment, and predictors of treatment response. We searched different online databases such as MEDLINE and EMBASE for studies on schizophrenia and CSF. Initial studies on cerebrospinalfluid in patients with schizophrenia revealed increased brain-blood barrier permeability with elevated total protein content, increased CSF-to-serum ratio for albumin, and intrathecal production of immunoglobulins in subgroups of patients. Analyses of metabolites in CSF suggest alterations within glutamatergic neurotransmission as well as monoamine and cannabinoid metabolism. Decreased levels of brain-derived neurotrophic factor and nerve growth factor in CSF of first-episode patients with schizophrenia reported in recent studies point to a dysregulation of neuroprotective and neurodevelopmental processes. Still, these findings must be considered as non-specific. A more profound characterization of the particular psychopathological profiles, the investigation of patients in the prodromal phase or within the first episode of schizophrenia promoting longitudinal investigations, implementation of different approaches of proteomics, and rigorous adherence to standard procedures based on international CSF guidelines are necessary to improve the quality of CSF studies in schizophrenia, paving the way for identification of syndrome-specific biomarker candidates. PMID:22173848
Vasic, Nenad; Connemann, Bernhard J; Wolf, Robert C; Tumani, Hayrettin; Brettschneider, Johannes
The role of blood-cerebrospinalfluid barrier (BCB) dysfunction in Alzheimer’s disease (AD) has been addressed but not yet established. We evaluated the BCB integrity in 179 samples of cerebrospinalfluid (CSF) retrospectively collected from AD patients and control cases using both CSF/serum albumin ratio (QAlb) and CSF secretory Ca2+-dependent phospholipase A2 (sPLA2) activity. These analyses were supplemented with the measurement of total tau, amyloid-?1–42 (A?1–42), and ubiquitin CSF levels. We found that due to its higher sensitivity, CSF sPLA2 activity could 1) discriminate AD from healthy controls and 2) showed BCB impairment in neurological control cases while QAlb could not. Moreover, the CSF sPLA2 activity measurement showed that around half of the AD patients were characterized by a BCB impairment. The BCB dysfunction observed in AD was independent from Mini-Mental State Examination score as well as CSF levels of total tau, A?1–42, and ubiquitin. Finally, the BCB dysfunction was not limited to any of the CSF biomarkers-based previously identified subgroups of AD. These results suggest that the BCB damage occurs independent of and probably precedes both A? and tau pathologies in a restricted subgroup of AD patients.
The acute effects of a 1-h -45 deg head-down tilt on continouously recorded cerebrospinalfluid pressure (PCSF) of conscious rats are studied in order to investigate the shift of blood volume into the thoracic cavity in microgravity. PCSF, evaluated in 15-min time blocks over a 3-h experiment, increased slightly (less than 0.05) during the first 30 min of a control hour at 0 deg. There was a transient increase for about 5 min immediately after tilt (-45 deg) that may have been due to head movement after the position change. PCSF was statistically unchanged (above 0.05) during the second (-45 deg) hour and the third (0 deg) recovery hour. It is shown that the dynamics of intracranial pressure regulation can accommodate the acute cephalad fluid shift after tilting.
Severs, Walter B.; Morrow, Bret A.; Keil, Lanny C.
Cerebrospinalfluid pressure (PCSF) was continuously measured in conscious male Sprague-Dawley rats gently restrained by a cotton towel. PCSF, evaluated in 15-min time blocks over a 3-h experiment, increased slightly (p less than 0.05) during the first 30 min of a control hour at 0 degree. There was a transient increase for about 5 min immediately after tilt (-45 degrees) that may have been due to head movement after the position change. However, PCSF was statistically unchanged (p greater than 0.05) during the 2nd (-45 degrees) hour and the 3rd (0 degree) recovery hour. The data show that the dynamics of intracranial pressure regulation can accommodate the acute cephalad fluid shift after tilting. PMID:1764005
Cerebral amyloid angiopathy is caused by deposition of the amyloid beta protein in the cerebral vasculature. In analogy to previous observations in Alzheimer disease, we hypothesized that analysis of amyloid beta(40) and beta(42) proteins in the cerebrospinalfluid might serve as a molecular biomarker. We observed strongly decreased cerebrospinalfluid amyloid beta(40) (p < 0.01 vs controls or Alzheimer disease)
M. M. Verbeek; H. P. H. Kremer; M. G. M. Olde Rikkert; M. E. Skehan; S. M. Greenberg
The lipid composition or the liver, spleen, brain, cerebellum and cerebrospinalfluid of a Gaucher disease type II patient who died at the age of 5 months was examined. The glycolipid analysis demonstrated a marked increase of total amounts not only in the peripheral tissues but also in the brain cerebellum and cerebrospinalfluid, with a prevalence of glucosylceramide. A
R. Gornati; B. Berra; G. Montorfano; C. Martini; G. Ciana; P. Ferrari; M. Romano; B. Bembi
Anaerobic meningitis in infants is rare, therefore a high index of clinical suspicion is essential as routine methods for processing cerebrospinalfluid (CSF) do not detect anaerobes and specific antimicrobial therapy is required. We present an infant with Escherichia coli meningitis where treatment-resistance developed in association with culture negative purulent CSF. These features should have alerted us to the presence of anaerobes, prompting a search for the causes of polymicrobial meningitis in infants. PMID:24118618
The aim of the present work is to analyze the cerebrospinalfluid proteomic profile, trying to find possible biomarkers of the effects of hypertension of the blood to CSF barrier disruption in the brain and their participation in the cholesterol and ?-amyloid metabolism and inflammatory processes. Cerebrospinalfluid (CSF) is a system linked to the brain and its composition can be altered not only by encephalic disorder, but also by systemic diseases such as arterial hypertension, which produces alterations in the choroid plexus and cerebrospinalfluid protein composition. 2D gel electrophoresis in cerebrospinalfluid extracted from the cistern magna before sacrifice of hypertensive and control rats was performed. The results showed different proteomic profiles between SHR and WKY, that ?-1-antitrypsin, apolipoprotein A1, albumin, immunoglobulin G, vitamin D binding protein, haptoglobin and ?-1-macroglobulin were found to be up-regulated in SHR, and apolipoprotein E, transthyretin, ?-2-HS-glycoprotein, transferrin, ?-1?-glycoprotein, kininogen and carbonic anhidrase II were down-regulated in SHR. The conclusion made here is that hypertension in SHR produces important variations in cerebrospinalfluid proteins that could be due to a choroid plexus dysfunction and this fact supports the close connection between hypertension and blood to cerebrospinalfluid barrier disruption. PMID:23401751
González-Marrero, Ibrahim; Castañeyra-Ruiz, Leandro; González-Toledo, Juan M; Castañeyra-Ruiz, Agustín; de Paz-Carmona, Hector; Castro, Rafael; Hernandez-Fernaud, Juan R; Castañeyra-Perdomo, Agustín; Carmona-Calero, Emilia M
Background Cerebrospinalfluid shunt infection can be recalcitrant. Recurrence is common despite appropriate therapy for the pathogens identified by culture. Improved diagnostic and therapeutic approaches are required, and culture-independent molecular approaches to cerebrospinalfluid shunt infections have not been described. Objectives To identify the bacteria and fungi present in cerebrospinalfluid from children with cerebrospinalfluid shunt infection using a high-throughput sequencing approach, and to compare those results to those from negative controls and conventional culture. Methods This descriptive study included eight children ?18 years old undergoing treatment for culture-identified cerebrospinalfluid shunt infection. After routine aerobic culture of each cerebrospinalfluid sample, deoxyribonucleic acid (DNA) extraction was followed by amplification of the bacterial 16S rRNA gene and the fungal ITS DNA region tag-encoded FLX-Titanium amplicon pyrosequencing and microbial phylogenetic analysis. Results The microbiota analyses for the initial cerebrospinalfluid samples from all eight infections identified a variety of bacteria and fungi, many of which did not grow in conventional culture. Detection by conventional culture did not predict the relative abundance of an organism by pyrosequencing, but in all cases, at least one bacterial taxon was detected by both conventional culture and pyrosequencing. Individual bacterial species fluctuated in relative abundance but remained above the limits of detection during infection treatment. Conclusions Numerous bacterial and fungal organisms were detected in these cerebrospinalfluid shunt infections, even during and after treatment, indicating diverse and recalcitrant shunt microbiota. In evaluating cerebrospinalfluid shunt infection, fungal and anaerobic bacterial cultures should be considered in addition to aerobic bacterial cultures, and culture-independent approaches offer a promising alternative diagnostic approach. More effective treatment of cerebrospinalfluid shunt infections is needed to reduce unacceptably high rates of reinfection, and this work suggests that one effective strategy may be reduction of the diverse microbiota present in infection.
Simon, Tamara D.; Pope, Christopher E.; Browd, Samuel R.; Ojemann, Jeffrey G.; Riva-Cambrin, Jay; Mayer-Hamblett, Nicole; Rosenfeld, Margaret; Zerr, Danielle M.; Hoffman, Lucas
Rabbits with experimentally induced pneumococcal meningitis were given single 25-mg/kg doses of apalcillin or cefpiramide. Mean percentages of the drug concentration in cerebrospinalfluid versus that in blood serum were 7.6% with apalcillin and 3.9% with cefpiramide. Bactericidal activity in cerebrospinalfluid resulted in mean reductions of from 4 to 5 log10 CFU/ml, and cerebrospinalfluid cultures became sterile for four of six animals treated with each drug.
We describe a patient with salmonella enteritidis meningitis and unknown HIV infection. Setting: A 14-bed adult intensive care unit in a tertiary hospital. The patient was brought to the emergency department with fever, nuchal rigidity and confusion. A first cerebrospinalfluid examination was non diagnostic. After a short period of improvement the patient developed septic shock. A second cerebrospinalfluid
Chrisostomos Katsenos; Nectarios Anastasopoulos; Maria Patrani; Costas Mandragos
We report the genetic, clinical, electrophysiological, and imaging studies in a family with bilateral striopallidodentate calcinosis (Fahr's disease). The intracerebral calcium deposits occurred before onset of the symptoms in the third decade of life. Progressive neurological deterioration occurred in the fifth decade of life in the proband. Cerebrospinalfluid homocarnosine, a central nervous system-specific peptide, was increased twofold in patients with autosomal dominant bilateral stripallidodentate calcinosis; in sporadic cases, there was no detectable homocarnosine and a decreased level of histidine. With advancing age, the amount of calcification increases, but it has not been determined if a critical amount must be reached before symptoms occur. Computerized tomography is superior to magnetic resonance imaging for radiological diagnosis. Despite diffuse striatal calcification, striatal 6-[18F]fluoro-L-dopa uptake did not reveal any difference between patients and control subjects, from which we infer persisting integrity of the nigrostriatal dopaminergic pathway. PMID:1586138
Manyam, B V; Bhatt, M H; Moore, W D; Devleschoward, A B; Anderson, D R; Calne, D B
Numerous studies have shown that Alzheimer's Disease (AD) pathology begins before the onset of clinical symptoms. Because therapies are likely to be more effective if they are implemented early in the disease progression, it is necessary to identify reliable biomarkers to detect AD pathology in the early stages of the disease, ideally in presymptomatic individuals. Recent research has identified three candidate cerebrospinalfluid (CSF) biomarkers that reflect AD pathology: amyloid beta, total tau protein (t-tau), and tau protein phosphorylated at AD-specific epitopes (p-tau). They are useful in supporting the AD diagnosis and have predictive value for AD when patients are in the stage of mild cognitive impairment (MCI). However, their predictive utility in cognitively healthy subjects is still being evaluated. We conducted a review of studies published between 1993 and 2011 and summarized their findings on the role of CSF biomarkers for AD in healthy elderly. PMID:23747874
Randall, Catherine; Mosconi, Lisa; de Leon, Mony; Glodzik, Lidia
The cerebrospinalfluid (CSF) has attracted renewed interest as an active signaling milieu that regulates brain development, homeostasis, and disease. Advances in proteomics research have enabled an improved characterization of the CSF from development through adulthood, and key neurogenic signaling pathways that are transmitted via the CSF are now being elucidated. Due to its immediate contact with neural stem cells in the developing and adult brain, the CSF's ability to swiftly distribute signals across vast distances in central nervous system is opening avenues to novel and exciting therapeutic approaches. In this review, we will discuss the development of the choroid plexus-CSF system, and review the current literature on how the CSF actively regulates mammalian brain development, behavior, and responses to traumatic brain injury.
This study investigated the role of two fatty acid ethanolamides, the endogenous cannabinoid anandamide and its structural analog oleoylethanolamide in sleep deprivation of human volunteers. Serum and cerebrospinalfluid (CSF) samples were obtained from 20 healthy volunteers before and after a night of sleep deprivation with an interval of about 12 months. We found increased levels of oleoylethanolamide in CSF (P = 0.011) but not in serum (P = 0.068) after 24 h of sleep deprivation. Oleoylethanolamide is an endogenous lipid messenger that is released after neural injury and activates peroxisome proliferator-activated receptor-alpha (PPAR-alpha) with nanomolar potency. Exogenous PPAR-alpha agonists, such as hypolipidemic fibrates and oleoylethanolamide, exert both neuroprotective and neurotrophic effects. Thus, our results suggest that oleoylethanolamide release may represent an endogenous neuroprotective signal during sleep deprivation. PMID:19137236
Numerous studies have shown that Alzheimer’s Disease (AD) pathology begins before the onset of clinical symptoms. Because therapies are likely to be more effective if they are implemented early in the disease progression, it is necessary to identify reliable biomarkers to detect AD pathology in the early stages of the disease, ideally in presymptomatic individuals. Recent research has identified three candidate cerebrospinalfluid (CSF) biomarkers that reflect AD pathology: amyloid beta (Aß42), total tau protein (t-tau), and tau protein phosphorylated at AD-specific epitopes (p-tau). They are useful in supporting the AD diagnosis and have predictive value for AD when patients are in the stage of mild cognitive impairment (MCI). However, their predictive utility in cognitively healthy subjects is still being evaluated. We conducted a review of studies published between 1993 and 2011 and summarized their findings on the role of CSF biomarkers for AD in healthy elderly.
Randall, Catherine; Mosconi, Lisa; de Leon, Mony; Glodzik, Lidia
Due to an ever aging society and growing prevalence of Alzheimer’s disease (AD), the challenge to meet social and health care system needs will become increasingly difficult. Unfortunately, a definite ante mortem diagnosis is not possible. Thus, an early diagnosis and identification of AD patients is critical for promising, early pharmacological interventions as well as addressing health care needs. The most advanced and most reliable markers are ?-amyloid, total tau and phosphorylated tau in cerebrospinalfluid (CSF). In blood, no single biomarker has been identified despite an intense search over the last decade. The most promising approaches consist of a combination of several blood-based markers increasing the reliability, sensitivity and specificity of the AD diagnosis. However, contradictory data make standardized testing methods in longitudinal and multi-center studies extremely difficult. In this review, we summarize a range of the most promising CSF and blood biomarkers for diagnosing AD.
A method for determining drug concentration relationships between plasma and cerebrospinalfluid (CSF) in rats is described. Continuous CSF samples were collected directly from the third anterior ventricle with an indwelling cannula inserted through the bregma point, and drug concentrations were determined by high-pressure liquid chromatography and radioimmunoassay micromethods. Three antibiotics with different abilities to cross the blood-CSF barrier (chloramphenicol, piperacillin, and gentamicin) were tested. This method was found to be reproducible for each drug even if the antibiotic levels were low and the sample volumes very small. Peak CSF concentrations occurred between 0.75 and 1.25 h after injection for all three antibiotics. Percent penetration values at 1 h were 50, 1.2, and 5.4% for chloramphenicol, piperacillin, and gentamicin, respectively.
Extracellular vesicles (EVs) are present in human cerebrospinalfluid (CSF), yet little is known about their protein composition. The aim of this study is to provide a comprehensive analysis of the proteome of CSF EVs by electron microscopy and high resolution tandem mass spectrometry (MS/MS) in conjunction with bioinformatics. We report an extensive catalog of 1315 proteins identified in EVs isolated from two different CSF pools by ultracentrifugation, including 230 novel EV proteins. Out of 1315 proteins, 760 were identified in both CSF pools and about 30% of those were also quantitatively enriched in the EV fraction versus the soluble CSF fraction. The proteome of CSF EVs was enriched in exosomal markers such as alix and syntenin-1, heat shock proteins and tetraspanins and contained a high proportion of brain-derived proteins (n=373). Interestingly, several known biomarkers for neurodegenerative diseases such as the amyloid precursor protein, the prion protein and DJ-1 were identified in the EV fractions. Our dataset represents the first comprehensive inventory of the EV proteome in CSF, underscoring the biomarker potential of this organelle. Further comparative studies on CSF EVs isolated from patients diagnosed with neurological disorders are warranted. Data are available via ProteomeXchange with identifier PXD000608. Biological significance In this study we analyzed the protein composition of extracellular vesicles isolated from pooled samples of human cerebrospinalfluid (CSF). CSF is a colorless fluid surrounding the brain and the spinal cord, important for the physiology of the central nervous system, ensuing mechanical protection, regulation of brain blood flow and elimination of byproducts of the brain. Since brain (patho)physiology is reflected in CSF, this biological fluid represents an ideal source of soluble and vesicle-based biomarkers for neurological diseases. Here we confirm the presence of exosome-like extracellular vesicles in CSF, underscoring a potential role in the physiology of the brain. These extracellular vesicles provide a rich source of candidate biomarkers, representing a brain "fluid biopsy". Most interestingly, the involvement of extracellular vesicles in transferring toxic proteins such as ?-synuclein and ?-amyloid has been postulated as one of the mechanisms involved in the spreading of neurodegeneration to different brain areas. In line with this, we show that human CSF extracellular vesicles contain prionogenic proteins such as the amyloid precursor protein and the prion protein. Delineating the protein composition of extracellular vesicles in CSF is a first and crucial step to comprehend their origin and their function in the central nervous system and to establish their biomarker potential. PMID:24769233
Chiasserini, Davide; van Weering, Jan R T; Piersma, Sander R; Pham, Thang V; Malekzadeh, Arjan; Teunissen, Charlotte E; de Wit, Heidi; Jiménez, Connie R
Cryptococcosis is a systemic fungal disease and meningitis is the most serious complication. The purpose of this study is to define problems related to its diagnosis and treatment. This is a retrospective analysis of 25 patients admitted from January 1978 to December 1981. All patients had cryptococcal neoformans meningitis proven by culture of cerebrospinalfluid. One patient had a predisposing illness, being on immunosuppressant therapy after a renal transplant 2 years ago. A progressively severe headache of recent onset was the most striking presentation. Fever was frequently absent as a symptom. Cranial nerve palsies were commonly seen. Impairment of consciousness and areflexia signified a poor prognosis as all four patients who died early in the course of treatment were comatose and two of them were areflexic on admission. In newly suspected cases at least 3 separate lumbar punctures are recommended as initial smears or cultures may be negative. Cerebral CT scans were abnormal in 12 patients and those with cerebral oedema or hydrocephalus had a poorer prognosis. Combined amphotericin B and 5-fluorocytosine therapy was the treatment of choice. If there is no relapse 3 years after completion of treatment, patients are considered as cured. Positive smears may remain for years after completion of treatment and retreatment is only indicated if the cultures are positive. Twenty patients are alive today and none of them have relapsed. One patient had vasculitis of both anterior cerebral arteries as a result of cryptococcal meningitis.
Enterovirus (EV) and human parechovirus (HPeV) are a major cause of infection in childhood. A rapid diagnostic test may improve the management of patients with EV and HPeV infection. The aim of this study is to evaluate the performance of the GeneXpert enterovirus assay (GXEA) for detection of EV RNA compared to a user-developed reverse-transcriptase (RT) quantitative real-time PCR (qPCR) in routine clinical practice. Also a RT-qPCR assay for detection of HPeV RNA in different clinical samples was developed and evaluated. Cerebrospinalfluid (CSF) from 232 patients suspected for meningitis was collected and tested for EV and HPeV using RT-qPCR assays. In parallel an aliquot of the samples was tested using the GXEA and viral culture. EV RNA was detected in 22 (19.0%) and 28 (24.1%) of 116 samples using the GXEA and RT-qPCR assay, respectively. EV was isolated from 10 of 116 (8.6%) samples by viral culture. GXEA had a sensitivity, specificity, positive predictive value and negative predictive value of 82.1%, 100%, 100% and 96.2%, respectively. In this study, molecular assays were superior to viral culture for detecting EV RNA in CSF. GXEA showed a high specificity but a lower sensitivity for the detection of EV RNA compared to the RT-qPCR assay. PMID:22024398
de Crom, S C M; Obihara, C C; van Loon, A M; Argilagos-Alvarez, A A; Peeters, M F; van Furth, A M; Rossen, J W A
Cerebrospinalfluid has shown itself to be an essential brain component during development. This is particularly evident at the earliest stages of development where a lot of research, performed mainly in chick embryos, supports the evidence that cerebrospinalfluid is involved in different mechanisms controlling brain growth and morphogenesis, by exerting a trophic effect on neuroepithelial precursor cells (NPC) involved in controlling the behaviour of these cells. Despite it being known that cerebrospinalfluid in mammals is directly involved in corticogenesis at fetal stages, the influence of cerebrospinalfluid on the activity of NPC at the earliest stages of brain development has not been demonstrated. Here, using "in vitro" organotypic cultures of rat embryo brain neuroepithelium in order to expose NPC to or deprive them of cerebrospinalfluid, we show that the neuroepithelium needs the trophic influence of cerebrospinalfluid to undergo normal rates of cell survival, replication and neurogenesis, suggesting that NPC are not self-sufficient to induce their normal activity. This data shows that cerebrospinalfluid is an essential component in chick and rat early brain development, suggesting that its influence could be constant in higher vertebrates. PMID:19540909
Martin, C; Alonso, M I; Santiago, C; Moro, J A; De la Mano, A; Carretero, R; Gato, A
Fast migrating cerebrosides (FMC) are derivatives of galactosylceramide (GalCer). The structures of the most hydrophobic FMC-5, FMC-6, and FMC-7 were determined by electrospray ionization linear ion-trap mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy complementing previous NMR spectroscopy and gas chromatography-mass spectrometry to be 3-O-acetyl-sphingosine-GalCer derivatives with galactose O-acetyl modifications. FMC-5 and FMC-6 are 3-O-acetyl-sphingosine-2,3,4,6-tetra-O-acetyl-GalCer with nonhydroxy and hydroxy-N-fatty-acids, while FMC-7 has an additional O-acetylation of the 2-hydroxy-fatty acid. The immuno-reactivity in human cerebrospinalfluid (CSF) to these acetylated glycolipids was examined in central nervous system (CNS) infectious disease, noninflammatory disorders, and multiple sclerosis (MS). Screening for lipid binding in MS and other neurological disease groups revealed that the greatest anti-hydrophobic FMC reactivity was observed in the inflammatory CNS diseases (meningitis, meningo-encephalitis, and subacute sclerosing panencephalitis). Some MS patients had increased reactivity with the hydrophobic FMCs and with glycoglycerophospholipid MfGL-II from Mycoplasma fermentans. The cross-reactivity of highly acetylated GalCer with microbial acyl-glycolipid raises the possibility that myelin-O-acetyl-cerebrosides, bacterial infection, and neurological disease are linked.
Podbielska, Maria; Dasgupta, Somsankar; Levery, Steven B.; Tourtellotte, Wallace W.; Annuk, Heidi; Moran, Anthony P.; Hogan, Edward L.
The present study aimed at profiling inflammatory cytokines for neurological and psychiatric diseases. A total of 86 patients with meningitis, multiple sclerosis, tension-type headache, idiopathic facial nerve palsy (IFNP), affective and schizophrenic disorders were tested for both, serum and cerebrospinalfluid (CSF) using a multiplexed cytokine ELISA for IFN-?, TNF-?, IL-1?, IL-2, IL-4, IL-5, IL-8/CXCL8, IL-10, IL12p70, IL-13 and IL-17. Cases with viral and bacterial meningitis had unequivocally higher cytokine concentrations in the CSF when compared with serum. Bacterial meningitis was unique by extremely elevated IL-17, TNF-? and IL-1?, indicating a plethora of inflammatory pathways, selectively activated in the CSF. In relapsing multiple sclerosis, IFN-? and IL-10 were elevated in both, serum and CSF, but IL-12p70, IL-5, IL-13, and TNF-? were more prominent in serum than in CSF. Qualitatively similar biomarker patterns were detected in patients with idiopathic facial nerve palsy and tension-type cephalgia. Affective and schizophrenic disorders clearly present with an inflammatory phenotype in the CSF and also serum, the cytokines determined were in general higher in schizophrenia. Except IFN-?, schizophrenic patients had higher IL-12p70 and a trend of higher IL-10 and IL-13 in serum suggesting a more prominent TH2-type counter regulatory immune response than in affective disorders. These differences were also mirrored in the CSF. Elevated IL-8 appears to be the most sensitive marker for inflammation in the CSF of all diseases studied, whereas TNF-? was restricted to peripheral blood. With the exception of IL-8, all but viral and bacterial meningitis, studied, displayed higher means of elevated lymphokine concentrations in the serum than in the CSF. This observation supports the concept of immunological crosstalk between periphery and intrathecal immunity in neurological and psychiatric diseases. PMID:25022963
Maxeiner, Horst-Guenter; Marion Schneider, E; Kurfiss, Sina-Tatjana; Brettschneider, Johannes; Tumani, Hayrettin; Bechter, Karl
Axonal damage is a prominent cause of disability and yet its pathogenesis is incompletely understood. Using a xenogeneic system, here we define the bioenergetic changes induced in rat neurons by exposure to cerebrospinalfluid samples from patients with multiple sclerosis compared to control subjects. A first discovery cohort of cerebrospinalfluid from 13 patients with multiple sclerosis and 10 control subjects showed that acute exposure to cerebrospinalfluid from patients with multiple sclerosis induced oxidative stress and decreased expression of neuroprotective genes, while increasing expression of genes involved in lipid signalling and in the response to oxidative stress. Protracted exposure of neurons to stress led to neurotoxicity and bioenergetics failure after cerebrospinalfluid exposure and positively correlated with the levels of neurofilament light chain. These findings were validated using a second independent cohort of cerebrospinalfluid samples (eight patients with multiple sclerosis and eight control subjects), collected at a different centre. The toxic effect of cerebrospinalfluid on neurons was not attributable to differences in IgG content, glucose, lactate or glutamate levels or differences in cytokine levels. A lipidomic profiling approach led to the identification of increased levels of ceramide C16:0 and C24:0 in the cerebrospinalfluid from patients with multiple sclerosis. Exposure of cultured neurons to micelles composed of these ceramide species was sufficient to recapitulate the bioenergetic dysfunction and oxidative damage induced by exposure to cerebrospinalfluid from patients with multiple sclerosis. Therefore, our data suggest that C16:0 and C24:0 ceramides are enriched in the cerebrospinalfluid of patients with multiple sclerosis and are sufficient to induce neuronal mitochondrial dysfunction and axonal damage. PMID:24893707
A 26-year-old previously healthy man presented with fever, urinary retention, nuchal rigidity, and hyperreflexia but with a clear sensorium. His initial spinal fluid results were consistent with aseptic meningitis from West Nile virus infection, and this was confirmed by serological studies on blood and cerebrospinalfluid. Computed tomography and magnetic resonance imaging studies were unremarkable. He received supportive care and urinary catheterization to prevent bladder injury from overdistension. He was discharged home without recurrence of urinary retention after five days of hospitalization. Therefore, this case report describes the first case of West Nile virus meningitis in a patient with the meningitis-retention syndrome.
Advances in magnetic resonance (MR) imaging techniques enable the accurate measurements of cerebrospinalfluid (CSF) flow in the human brain. In addition, image reconstruction tools facilitate the collection of patient-specific brain geometry data such as the exact dimensions of the ventricular and subarachnoidal spaces (SAS) as well as the computer-aided reconstruction of the CSF-filled spaces. The solution of the conservation of CSF mass and momentum balances over a finite computational mesh obtained from the MR images predict the patients' CSF flow and pressure field. Advanced image reconstruction tools used in conjunction with first principles of fluid mechanics allow an accurate verification of the CSF flow patters for individual patients. This paper presents a detailed analysis of pulsatile CSF flow and pressure dynamics in a normal and hydrocephalic patient. Experimental CSF flow measurements and computational results of flow and pressure fields in the ventricular system, the SAS and brain parenchyma are presented. The pulsating CSF motion is explored in normal and pathological conditions of communicating hydrocephalus. This paper predicts small transmantle pressure differences between lateral ventricles and SASs (approximately 10 Pa). The transmantle pressure between ventricles and SAS remains small even in the hydrocephalic patient (approximately 30 Pa), but the ICP pulsatility increases by a factor of four. The computational fluid dynamics (CFD) results of the predicted CSF flow velocities are in good agreement with Cine MRI measurements. Differences between the predicted and observed CSF flow velocities in the prepontine area point towards complex brain-CSF interactions. The paper presents the complete computational model to predict the pulsatile CSF flow in the cranial cavity. PMID:17278586
Linninger, Andreas A; Xenos, Michalis; Zhu, David C; Somayaji, MahadevaBharath R; Kondapalli, Srinivasa; Penn, Richard D
This book on cerebrospinalfluid (CSF) proteins is primarily focused on immunoglobulins. The book was written as an extension of a meeting on multiple sclerosis to provide a more extensive consideration of the CSF.
Rickettsial infections are common in southern Europe and the most frequent and lethal type is Mediterranean spotted fever, caused by Rickettsia conorii. The disease is usually characterised by the classical triad of fever, eschar and rash, and is generally a mild disease in children. Complications including neurological involvement are rarely described. We report an unusual case of meningitis in an 18-year-old man, presenting during summer with fever and persistent headache. The cerebrospinalfluid analysis revealed increased cellularity (107 cells/?L), hypoglycorrhachia (50% of glycaemia) and hyperproteinorrhachia (284 mg/dL). Rickettsial infection was confirmed by serology and the patient was treated with doxycycline, with a favourable outcome. The patient's pet squirrel and/or associated vectors might be involved in the transmission of Rickettsia spp. This case underlines the importance of a high clinical suspicion and the benefits of early empirical treatment when facing compatible epidemiological contexts. PMID:24614778
In three out of five patients with low cerebrospinalfluid thiamine concentrations, the 5-hydroxyindoleacetic acid (5HIAA) values also were low. All patients received thiamine replacement therapy; they underwent a second lumbar puncture after 13, 6, 7, 5 and 45 days of treatment. In all patients blood and cerebrospinalfluid thiamine values rose after treatment. In those patients with initially low CSF 5HIAA, thiamine treatment increased 5HIAA markedly.
Botez, M I; Young, S N; Bachevalier, J; Gauthier, S
Chromatography under acid dissociating conditions in conjunction with radioimmunoassay has been employed to investigate the nature of peptides related to opiocortin in human cerebrospinalfluid. Samples of cerebrospinalfluid (CSF) were collected for chromatography from 15 patients prior to air encephalography. 2 patients had pituitary dependent Cushing’s disease, 3 non-endocrine neurological disease and 10 non-ACTH related pituitary disease. The column
Lorraine McLoughlin; P. J. Lowry; Sally J. Ratter; J. Hope; G. M. Besser; Lesley H. Rees
Electrodiagnostic testing (electromyography, electroneuronography, and blink reflex) and cerebrospinalfluid (CSF) examination (cell count, immunoglobulins, and antigen-specific intrathecal immunoglobulin G synthesis against herpes simplex virus, varicella zoster virus, cytomegalovirus, and Borrelia burgdorferi sensu latu) were performed in 56 patients with Bell's palsy. The CSF was normal in 45 patients and abnormal in 11 patients. Acute borreliosis was the most common specific pathological CSF finding (4 of 11). Electromyography revealed abolished volitional activity in 22% of patients with normal CSF and in 36% with pathological CSF. Electroneuronographic tests with an amplitude decrease of more than 90% on the affected side or abolished responses were found in 20% of patients with normal CSF and in 18% with pathological CSF. Abolished orbicularis oculi reflexes were seen in 67% of patients with normal CSF and in 82% with pathological CSF Concerning electrodiagnostic testing, no statistically significant difference between patients with normal and abnormal CSF was found, so we conclude that electrodiagnostic testing has no indicative value for abnormal CSF in Bell's palsy. PMID:11407851
Birkmann, C; Bamborschke, S; Halber, M; Haupt, W F
Objective?To describe our experience of cerebrospinalfluid (CSF) rhinorrhea management. Design?Retrospective. Setting?Charing Cross Hospital, London, a tertiary referral center. Participants?Fifty-four patients with CSF rhinorrhea managed from 2003 to 2011. Main outcome measures?Surgical technique; Recurrence. Results?Etiologically, 36 were spontaneous and 18 traumatic. Eight patients with spontaneous and two with traumatic leaks had previous failed repairs in other units. Success rates after first and second surgery were 93% and 100%, respectively. Mean follow-up was 21 months. Four patients, all of spontaneous etiology, had recurrences; three of these underwent successful second repair with three layered technique, and the fourth had complete cessation of the leak after gastric bypass surgery and subsequent weight reduction. Adaptation of anatomic three-layered repair since then averted any further failure in the following 7 years. Mean body mass index was 34.0 kg/m(2) in spontaneous and 27.8 kg/m(2) in traumatic cases (p?0.05). Fifty percent of spontaneous leaks were from the cribriform plate, 22% sphenoid, 14% ethmoid, and 14% frontal sinus. In the traumatic CSF leak group: 33.3% were from the cribriform plate, 33.3% sphenoid, 22.2% ethmoid, and 11.1% frontal. Conclusion?Endoscopic CSF fistula closure is a safe and effective operation. All sites of leak can be accessed endoscopically. We recommend the use of an anatomic three-layered closure in difficult cases. PMID:24436890
Virk, Jagdeep Singh; Elmiyeh, Behrad; Saleh, Hesham A
The maintenance of brain extracellular glutamate (Glu) at levels below its excitotoxic threshold is performed by Glu transporters present on glia and neurons as well as on brain capillary endothelial cells which remove brain Glu into blood. The feasibility of accelerating the naturally occurring brain-to-blood Glu efflux was studied using paradigms based on the fate of Glu present in the cerebrospinalfluid or infused into the brain ventricles and monitored before, during, and after decreasing blood Glu levels with pyruvate and oxaloacetate, the respective Glu co-substrates of the blood resident enzymes glutamate-pyruvate transaminase and glutamate-oxaloacetate transaminase. Results from cerebroventricular perfusions with [3H]Glu, intracerebroventricular injections of [3H]Glu, and measurements of the basal CSF Glu levels point out to the same conclusion that the intravenous administration of pyruvate and oxaloacetate which decreases blood Glu levels accelerates the brain-to-blood Glu efflux. We conclude that the brain extracellular Glu levels can be controlled in part by the blood Glu levels. The results may provide not only a rational explanation for the inhibition of Glu release and neuroprotective effects of parentally administered pyruvate in hemorrhagic shock and forebrain ischemia but could also outline a potential strategy for the removal of excess Glu in various neurodegenerative disorders. PMID:12969259
Gottlieb, Miroslav; Wang, Yin; Teichberg, Vivian I
The caudate nucleus has the highest acetylcholinesterase (AChE) activity in the brain and it has been shown that autopsied brain tissue of patients with Huntington's disease (HD) have reduced levels of acetylcholine. Because of these findings, the cholinergic function in HD was studied by measuring cerebrospinalfluid (CSF) choline levels and AChE activity during a randomized, double-blind, cross-over, placebo-controlled clinical trial of isoniazid. While mean choline levels adjusted for age were lower compared with controls (P = 0.0007), AChE activity did not differ between HD patients and normal controls. Treatment with isoniazid had no significant effect on CSF choline levels or CSF AChE activity. CSF AChE activity showed a statistically significant increase with advancing age. The reduced level of choline in CSF of HD patients may reflect either a defect in choline transport into the brain or a decrease of choline-phospholipid output from the brain. PMID:2146369
We examined acetylcholinsterase (AChE) activity and choline levels in cerebrospinalfluid (CSF) in 16 patients with idiopathic Parkinson's disease and 9 control subjects of corresponding age: 8 were untreated Parkinson's patients; 4 were treated with carbidopa-levodopa (100/1,000 mg/day) for 20 +/- 3 months; and 4 were treated with carbidopa-levodopa (110/1,100 mg/day) for 28 +/- 18 months plus amantadine (200 mg/day) for 16 +/- 8 months. CSF choline levels (nmol/ml) were 2.97 +/- 0.79 (control subjects); 1.31 +/- 0.29 (untreated patients); 1.00 +/- 0.29 (carbidopa-levodopa treated); and 1.26 +/- 0.19 (carbidopa-levodopa/amantadine treated). Choline levels were significantly lower in untreated and treated patients compared to control subjects (p = 0.0001). AChE activity did not differ in Parkinson's disease patients as compared to control subjects. The reduced level of choline in CSF may reflect a deficit in choline transport into the brain or a decrease of choline-phospholipid output from the brain. PMID:2360805
1. Objectives Parkinson's disease (PD) afflicts approximately 1-2% of the population over 50 years of age. No cures or effective modifying treatments exist and clinical diagnosis is currently confounded by a lack of definitive biomarkers. We sought to discover potential biomarkers in the cerebrospinalfluid (CSF) of neuropathologically confirmed PD cases. 2. Methods We compared postmortem ventricular CSF (V-CSF) from PD and normal control (NC) subjects using two-dimensional difference gel electrophoresis (2D-DIGE). Spots exhibiting a 1.5-fold or greater difference in volume between PD patients and controls were excised from the 2D gels, subjected to tryptic digestion and identification of peptides assigned using mass spectrometric/data bank correlation methods. 3. Results Employing this strategy six molecules: fibrinogen, transthyretin, apolipoprotein E, clusterin, apolipoprotein A-1 and glutathione-S-transferase-Pi were found to be different between PD and NC populations. 4: Discussion These molecules have been implicated in PD pathogenesis. Combining biomarker data from multiple laboratories may create a consensus panel of proteins that may serve as a diagnostic tool for this neurodegenerative disorder.
Maarouf, Chera L.; Beach, Thomas G.; Adler, Charles H.; Shill, Holly A.; Sabbagh, Marwan N.; Wu, Terence; Walker, Douglas G.; Kokjohn, Tyler A.; Roher, Alex E.
Background Interleukin (IL)-6 is recognised as an important cytokine involved in inflammatory diseases of the central nervous system (CNS). Objective To perform a large retrospective study designed to test cerebrospinalfluid (CSF) IL-6 levels in the context of neurological diseases, and evaluate its usefulness as a biomarker to help discriminate multiple sclerosis (MS) from other inflammatory neurological diseases (OIND). Patients and Methods We analyzed 374 CSF samples for IL-6 using a quantitative enzyme-linked immunosorbent assay. Groups tested were composed of demyelinating diseases of the CNS (DD, n?=?117), including relapsing-remitting MS (RRMS, n?=?65), primary progressive MS (PPMS, n?=?11), clinically isolated syndrome (CIS, n?=?11), optic neuritis (ON, n?=?30); idiopathic transverse myelitis (ITM, n?=?10); other inflammatory neurological diseases (OIND, n?=?35); and non-inflammatory neurological diseases (NIND, n?=?212). Differences between groups were analysed using Kruskal?Wallis test and Mann?Whitney U-test. Results CSF IL-6 levels exceeded the positivity cut-off of 10 pg/ml in 18 (51.4%) of the 35 OIND samples, but in only three (3.9%) of the 76 MS samples collected. CSF IL-6 was negative for all NIND samples tested (0/212). IL-6 cut-off of 10 pg/ml offers 96% sensitivity to exclude MS. Conclusion CSF IL-6 may help to differentiate MS from its major differential diagnosis group, OIND.
Neurofibrillary tangles (NFTs) have been shown in 20% of subacute sclerosing panencephalitis (SSPE) cases. NFTs contain paired helical filaments formed by hyperphosphorylated tau. The intraneuronal tau metabolism and the rate of formation of paired helical filaments can be regulated by interactions between tau and isoforms of Apolipoprotein E (Apo E). Tau binds in vitro to Apo E3, interferes with the hyperphosphorylation of tau and may reduce the formation of NFTs. We investigated cerebrospinalfluid (CSF) Apo E levels in SSPE (n=37) and age-matched control (n=38) groups. The median level of total Apo E and Apo E4 were lower in the SSPE than the control group (p<0.001 and p=0.002). On the other hand, median Apo E3 level (0.28±0.23 ?g/ml) was higher in the SSPE group (p<0.001). Such elevated levels of ApoE3 might play a role in controlling the formation of NFTs in SSPE. Because NFT-associated neurodegeneration is a slow process, comparison of the long-term clinical course of SSPE cases with high and low Apo E3 levels might provide further understanding or the role of these molecules in this disease, and help the planning of neuroprotective treatment. PMID:21788110
Oxygen causes an increase in the longitudinal relaxation rate of tissues through its T1-shortening effect owing to its paramagnetic properties. Due to such effects, MRI has been used to study oxygen-related signal intensity changes in various body parts including cerebrospinalfluid (CSF) space. Oxygen enhancement of CSF has been mainly studied using MRI sequences with relatively longer time resolution such as FLAIR, and T1 value calculation. In this study, fifteen healthy volunteers were scanned using fast advanced spin echo MRI sequence with and without inversion recovery pulse in order to dynamically track oxygen enhancement of CSF. We also focused on the differences of oxygen enhancement at sulcal and ventricular CSF. Our results revealed that CSF signal after administration of oxygen shows rapid signal increase in both sulcal CSF and ventricular CSF on both sequences, with statistically significant predominant increase in sulcal CSF compared with ventricular CSF. CSF is traditionally thought to mainly form from the choroid plexus in the ventricles and is absorbed at the arachnoid villi, however, it is also believed that cerebral arterioles contribute to the production and absorption of CSF, and controversy remains in terms of the precise mechanism. Our results demonstrated rapid oxygen enhancement in sulcal CSF, which may suggest inhaled oxygen may diffuse into sulcal CSF space rapidly probably due to the abundance of pial arterioles on the brain sulci.
Mehemed, Taha M.; Fushimi, Yasutaka; Okada, Tomohisa; Yamamoto, Akira; Kanagaki, Mitsunori; Kido, Aki; Fujimoto, Koji; Sakashita, Naotaka; Togashi, Kaori
Central nervous system (CNS) involvement is a common and important complication in systemic lupus erythematosus. The mechanisms for CNS involvement are poorly understood and reliable diagnostic procedures are lacking. Pairs of serum and cerebrospinalfluid (CSF) specimens from 17 patients with clinical and serological manifestations of systemic lupus erythematosus were analysed. All 11 patients with definite or suspect clinical CNS disorder revealed some kind of abnormality in the CSF, in contrast to three of seven systemic lupus erythematosus patients without CNS disorder. The most prominent findings in systemic lupus erythematosus patients with CNS disorder were immune aberrations with oligoclonal bands on agarose isoelectric focusing (AIF) and elevation of IgG and IgM index, probably reflecting intrathecal production of IgG and IgM respectively. Intrathecal production of antiviral antibodies was found in four of 12 patients by AIF followed by immunofixation and subsequent autoradiography. An enzyme-linked immunoabsorbent assay (ELISA) could not detect autoantibodies against structural brain antigens. Images
Oxygen causes an increase in the longitudinal relaxation rate of tissues through its T1-shortening effect owing to its paramagnetic properties. Due to such effects, MRI has been used to study oxygen-related signal intensity changes in various body parts including cerebrospinalfluid (CSF) space. Oxygen enhancement of CSF has been mainly studied using MRI sequences with relatively longer time resolution such as FLAIR, and T1 value calculation. In this study, fifteen healthy volunteers were scanned using fast advanced spin echo MRI sequence with and without inversion recovery pulse in order to dynamically track oxygen enhancement of CSF. We also focused on the differences of oxygen enhancement at sulcal and ventricular CSF. Our results revealed that CSF signal after administration of oxygen shows rapid signal increase in both sulcal CSF and ventricular CSF on both sequences, with statistically significant predominant increase in sulcal CSF compared with ventricular CSF. CSF is traditionally thought to mainly form from the choroid plexus in the ventricles and is absorbed at the arachnoid villi, however, it is also believed that cerebral arterioles contribute to the production and absorption of CSF, and controversy remains in terms of the precise mechanism. Our results demonstrated rapid oxygen enhancement in sulcal CSF, which may suggest inhaled oxygen may diffuse into sulcal CSF space rapidly probably due to the abundance of pial arterioles on the brain sulci. PMID:24956198
Mehemed, Taha M; Fushimi, Yasutaka; Okada, Tomohisa; Yamamoto, Akira; Kanagaki, Mitsunori; Kido, Aki; Fujimoto, Koji; Sakashita, Naotaka; Togashi, Kaori
Background: Ventriculoperitoneal (VP) shunts are among the most frequently performed operations in the management of hydrocephalus. Hepatic cerebrospinalfluid (CSF) pseudocyst is a rare but important complication in patients with a VP shunt insertion. In addition to presenting our own case, we performed a PubMed search to comprehensively illustrate the predisposing factors, clinical picture, diagnostic methods, and surgical treatment. This article represents an update for this condition. Case Description: A 40-year-old male was admitted to a hospital complaining of fever, abdominal distention, and pain. He had undergone a VP shunt for communicating hydrocephalus caused by a head trauma one year earlier. Laboratory studies showed liver enzymes alterations, and imaging studies demonstrated a well-defined intraaxially hepatic cyst with the shunt catheter placed inside. Staphylococcus epidermis was cultured via CSF. After removing the VP shunt and an adequate antibiotic treatment, the complication of hepatic CSF pseudocyst was resolved. Conclusion: Hepatic CSF pseudocyst is a rare complication of a VP shunt. Once the diagnosis is verified and if the CSF is sterile, just simply remove the peritoneal catheter and reposition a new one in the abdomen. We believe that it is not necessary to remove or aspirate the hepatic intraaxial pseudocyst, because of the risk of bleeding. In case of CSF infection, the VP shunt can be removed and/or an external derivation can be made, and after treatment with antibiotics, a new VP shunt is placed in the opposite side of the peritoneum.
Dabdoub, Carlos B.; Fontoura, Emilio A.; Santos, Egmond A.; Romero, Paulo C.; Diniz, Cristiano A.
Although heavy metal ions are known to be toxic to the central nervous system (CNS), the mechanisms by which the CNS may protect itself from initial challenges of such toxic ions is unknown. The choroid plexus is the principal site of formation of the cerebrospinalfluid (CSF) which bathes the brain. We have determined in rats and rabbits that after intraperitoneal administration of lead, cadmium, mercury, and arsenic compounds, these toxic metal ions accumulated in the lateral choroid plexus at concentrations of Pb, Hg, and As that were 70-, 95-, and 40-fold higher, respectively, than those found in CSF. Cd was not detected in the CSF. In addition, concentrations of these heavy metal ions were found to be many fold greater in the choroid plexus than in the brain or blood. The accumulation of Pb in the choroid plexus was dose-dependent and time-related. When the choroid plexus was preincubated, in vitro, with ouabain (1.5 mM), the uptake of Cd from the CSF side of the choroid plexus was inhibited 57%. Cadmium metallothionein was not found in the choroid plexus. Whereas the concentration of reduced glutathione in the choroid plexus was less than that in the brain cortex, the concentration of cysteine was fourfold greater. The lateral choroid plexus sequesters Pb, Cd, As, and Hg. It appears to be one of the important mechanisms that protects the CSF and the brain from the fluxes of toxic heavy metals in the blood.
Transclival meningoceles and primary spontaneous cerebrospinalfluid (CSF) leaks at the clivus are extremely rare lesions and only few of them have been reported in the literature. We report here six cases of transclival primary spontaneous CSF leaks through the clivus. A retrospective case study was performed. We reviewed six cases involving sinonasal CSF leaks located at the clivus treated between 1997 and 2009. Presenting symptoms, duration of symptoms, defect size, site of defect, surgical approach and technique of defect closure, intraoperative complications, postoperative complications, and recurrences are discussed. All CSF leaks were located in the upper central part of the clivus. two of six patients showed signs of increased intracranial pressure (ICP) including arachnoid pits and/or empty sella. For three patients a purely transnasal approach was used with multilayer reconstruction using a nonvascularized graft, and three patients underwent a transnasal transseptal approach with a multilayer reconstruction, with nasoseptal flap. No recurrences of CSF leaks at clivus or other sites were observed to date with a mean follow-up of 10.3 years (range, 3–15 years). Spontaneous CSF rhinorrhea located at the clivus is an extremely rare condition. To date, only eight cases have been described. Here, we report the largest group of six consecutive cases. Irrespective of the used reconstruction technique in all cases a 100% closure rate was achieved. However, identification of increased ICP is an essential aspect and this condition should be treated either medically or surgically.
The frequent co-occurrence of Alzheimer disease (AD) pathology in patients with normal pressure hydrocephalus suggests a possible link between ventricular dilation and AD. If enlarging ventricles serve as a marker of faulty cerebrospinalfluid (CSF) clearance mechanisms, then a relationship may be demonstrable between increasing ventricular volume and decreasing levels of amyloid beta peptide (A?) in CSF in preclinical and early AD. CSF biomarker data (A?, tau, and phosphorylated tau) as well as direct measurements of whole brain and ventricular volumes were obtained from the Alzheimer's Disease Neuroimaging Initiative dataset. The ratio of ventricular volume to whole brain volume was derived as a secondary independent measure. Baseline data were used for the group analyses of 288 subjects classified as being either normal (n=87), having the syndrome of mild cognitive impairment (n=136), or mild AD (n=65). Linear regression models were derived for each biomarker as the dependent variable, using the MRI volume measures and age as independent variables. For controls, ventricular volume was negatively associated with CSF A? in APOE ?4 positive subjects. A different pattern was seen in AD subjects, in whom ventricular volume was negatively associated with tau, but not A? in ?4 positive subjects. Increased ventricular volume may be associated with decreased levels of CSF A? in preclinical AD. The basis for the apparent effect of APOE ?4 genotype on the relationship of ventricular volume to A? and tau levels is unknown, but could involve altered CSF-blood-brain barrier function during the course of disease.
Ott, Brian R.; Cohen, Ronald A.; Gongvatana, Assawin; Okonkwo, Ozioma C.; Johanson, Conrad E.; Stopa, Edward G.; Donahue, John E.; Silverberg, Gerald D.
Objective?To describe our experience of cerebrospinalfluid (CSF) rhinorrhea management. Design?Retrospective. Setting?Charing Cross Hospital, London, a tertiary referral center. Participants?Fifty-four patients with CSF rhinorrhea managed from 2003 to 2011. Main outcome measures?Surgical technique; Recurrence. Results?Etiologically, 36 were spontaneous and 18 traumatic. Eight patients with spontaneous and two with traumatic leaks had previous failed repairs in other units. Success rates after first and second surgery were 93% and 100%, respectively. Mean follow-up was 21 months. Four patients, all of spontaneous etiology, had recurrences; three of these underwent successful second repair with three layered technique, and the fourth had complete cessation of the leak after gastric bypass surgery and subsequent weight reduction. Adaptation of anatomic three-layered repair since then averted any further failure in the following 7 years. Mean body mass index was 34.0 kg/m2 in spontaneous and 27.8 kg/m2 in traumatic cases (p?0.05). Fifty percent of spontaneous leaks were from the cribriform plate, 22% sphenoid, 14% ethmoid, and 14% frontal sinus. In the traumatic CSF leak group: 33.3% were from the cribriform plate, 33.3% sphenoid, 22.2% ethmoid, and 11.1% frontal. Conclusion?Endoscopic CSF fistula closure is a safe and effective operation. All sites of leak can be accessed endoscopically. We recommend the use of an anatomic three-layered closure in difficult cases.
Virk, Jagdeep Singh; Elmiyeh, Behrad; Saleh, Hesham A.
Moxifloxacin, an 8-methoxyquinolone with broad-spectrum activity in vitro, was studied in the rabbit model of Escherichia coli meningitis. The purposes of this study were to evaluate the bactericidal effectiveness and the pharmacodynamic profile of moxifloxacin in cerebrospinalfluid (CSF) and to compare the bactericidal activity with that of ceftriaxone and meropenem therapy. After induction of meningitis, animals were given single
VIOLETA RODRIGUEZ-CERRATO; CYNTHIA C. MCCOIG; IAN C. MICHELOW; FARYAL GHAFFAR; HASAN S. JAFRI; ROBERT D. HARDY; CHETAN PATEL; KURT OLSEN; GEORGE H. MCCRACKEN
We have evaluated a new set of primers (TRC4) in comparison with the IS6110 primers commonly used in PCR to detect tuberculous meningitis among children. The levels of concordance between the results of IS6110 PCR and TRC4 PCR with cerebrospinalfluid specimens from patients with clinically confirmed tuberculous meningitis were 80 and 86%, respectively. Results with the two primer sets
SUJATHA NARAYANAN; VIJAYALAKSHMI PARANDAMAN; P. R. Narayanan; P. Venkatesan; C. Girish; S. Mahadevan; SARALA RAJAJEE
Aims The aim of this study was to define the relationship between unbound propofol concentrations in plasma and total drug concentrations in human cerebrospinalfluid (CSF), and to determine whether propofol exists in the CSF in bound form. Methods Forty-three patients (divided into three groups) scheduled for elective intracranial procedures and anaesthetized by propofol target control infusion (TCI) were studied. Blood and CSF samples (taken from the radial artery, and the intraventricular drainage, respectively) from group I (17 patients) were used to investigate the relationship between unbound propofol concentration in plasma and total concentration of the drug in CSF. CSF samples taken from group II (18 patients) were used to confirm the presence of the bound form of propofol in this fluid. The CSF and blood samples taken from group III (eight patients) were used to monitor the course of free and bound CSF propofol concentrations during anaesthesia. Results For group I patients the mean (and 95% confidence interval) total plasma propofol concentration was 6113 (4971, 7255) ng ml?1, the mean free propofol concentration in plasma was 63 (42, 84) ng ml?1, and the mean total propofol concentration in CSF was 96 (76, 116) ng ml?1 (P < 0.05 for the difference between the last two values). For group II patients the fraction of free propofol in CSF was 31 (26, 37)%. For group III patients the fraction of free propofol in CSF during TCI was almost constant (about 36%). Conclusions The unbound propofol concentration in plasma was not equal to its total concentration in CSF and cannot be directly related to the drug concentration in the brain. Binding of propofol to components of the CSF may be an additional mechanism regulating the transport of the drug from blood into CSF.
Dawidowicz, Andrzej L; Kalitynski, Rafal; Fijalkowska, Anna
Acute amebic meningoencephalitis caused by free-living amebae naegleria fowleri is extremely rare and uniformly fatal with only seven survivals reported till date. An interesting case of naegleria meningitis diagnosed by wet mount cytology of cerebrospinalfluid (CSF) and treated with amphoterecin B, rifampicin and ornidazole with complete recovery is presented. In cases of suspected pyogenic meningitis, if CSF staining, antigen detection or culture is negative for bacteria, a wet mount cytology of CSF for naegleria is suggested. Early treatment with amphoterecin B and rifampicin may improve survival. PMID:12577098
Jain, R; Prabhakar, S; Modi, M; Bhatia, R; Sehgal, R
A 66-year-old woman was admitted to our hospital with recurrent meningitis. She presented with 10 episodes of meningitis in 10 months. Examination of cerebrospinalfluid demonstrated pleocytosis, with neutrophils dominant at the early stage, and lymphocytes dominant at the late stage. Mollaret cells were found and the level of IL-6 was increased in cerebrospinalfluid. Several antibiotics and antiviral agents failed to prevent relapse. However, colchicine therapy successfully prevented the recurrence of meningitis. Genetic testing for familial Mediterranean fever (FMF) showed a mutation in the MEFV gene. It is difficult to diagnose the cause of Mollaret's meningitis in some patients. FMF, neuro-Behçet's disease, and neuro-Sweet disease should be included in the differential diagnosis of recurrent meningitis. In addition, colchicine therapy can prevent the relapse of meningitis in such cases. PMID:24583586
Background: The gold standard for diagnosis of meningitis depends on cerebrospinalfluid (CSF) examination by microscopy, biochemistry, and culture, which require an experienced microscopist and laboratory support. We conducted this study to determine if urinary reagent strip is useful to make a semi-quantitative assessment of protein, glucose, and presence of leukocyte esterase in CSF. Materials and Methods: All consecutive CSF samples were evaluated in a blinded fashion. CSF was tested using Combur-10 urinary reagent strip as an index test, and CSF microscopy and biochemistry as reference standards. Combur-10 (Boehringer Mannheim) is a urinary reagent strip used to estimate ten parameters including protein, glucose, and leukocytes. We estimated diagnostic accuracy of each index test using corresponding cut-off levels (glucose 1 + vs. CSF glucose >50 mg/dL; protein 1 + and 2 + vs. CSF protein >30 mg/dL and >100 mg/dL; leukocyte esterase positivity vs. >10 granulocytes in CSF sample). We constructed receiver operating curves (ROC) to evaluate overall performance of index tests and estimated area under the curve (AUC). Results: CSF samples of 75 patients were included in the study. All the three indicator tests (CSF cells, protein, and glucose) were normal in 17 (22.6%) samples. Of the three tests, diagnostic accuracy of protein estimation (1 + or more on reagent strip) was best for detection of CSF proteins greater than 30 mg/dL [sensitivity 98.1% (95% CI 90.1-100%); specificity 57.1% (95% CI 34-78.2%)], with AUC of 0.97. Sensitivity and specificity for 2 + on reagent strip and CSF protein > 100 mg/dL were 92.6% (95% CI 75.1-99.1) and 87.5% (95% CI 74.8-95.3), respectively, with AUC of 0.96 (95% CI 0.92-1.01). Leukocyte esterase positivity by test strip had a sensitivity of 85.2 (95% CI 66.3-95.8%) and specificity of 89.6 (95% CI 77.3-96.5%) for detection of CSF granulocytes of more than 10/mm3. Conclusion: Existing urinary reagent strips can be used to diagnose meningitis in low-resource settings.
MicroRNAs are short non-coding RNAs that modulate gene expression by translational repression. Because of their high stability in intracellular as well as extracellular environments, miRNAs have recently emerged as important biomarkers in several human diseases. However, they have not been tested in the cerebrospinalfluid (CSF) of HIV-1 positive individuals. Here, we present results of a study aimed at determining the feasibility of detecting miRNAs in the CSF of HIV-infected individuals with and without encephalitis (HIVE). We also evaluated similarities and differences between CSF and brain tissue miRNAs in the same clinical setting. We utilized a high throughput approach of miRNA detection arrays and identified differentially expressed miRNAs in the frontal cortex of three cases each of HIV+, HIVE, and HIV? controls, and CSF of ten HIV-positive and ten HIV-negative individuals. For the CSF samples, the group of HIV+ individuals contained nine cases of HIV-Associated Neurological Disorders (HAND) and, among those, four had HIVE. All the HIV-negative samples had non-viral acute disseminate encephalomyelitis. A total of 66 miRNAs were found differentially regulated in HIV+ compared to HIV? groups. The greatest difference in miRNA expression was observed when four cases of HIVE were compared to five non-HIVE cases, previously normalized with the HIV-negative group. After statistical analyses, eleven miRNAs were fund significantly up-regulated in HIVE. Although more clinical samples should be examined, this work represents the first report of CSF miRNAs in HIV-infection and offers the basis for future investigation.
During the last decade, the epidemiology of WNV in humans has changed in the southern regions of Europe, with high incidence of West Nile fever (WNF) cases, but also of West Nile neuroinvasive disease (WNND). The lack of human vaccine or specific treatment against WNV infection imparts a pressing need to characterize indicators associated with neurological involvement. By its intimacy with central nervous system (CNS) structures, modifications in the cerebrospinalfluid (CSF) composition could accurately reflect CNS pathological process. Until now, few studies investigated the association between imbalance of CSF elements and severity of WNV infection. The aim of the present study was to apply the iTRAQ technology in order to identify the CSF proteins whose abundances are modified in patients with WNND. Forty-seven proteins were found modified in the CSF of WNND patients as compared to control groups, and most of them are reported for the first time in the context of WNND. On the basis of their known biological functions, several of these proteins were associated with inflammatory response. Among them, Defensin-1 alpha (DEFA1), a protein reported with anti-viral effects, presented the highest increasing fold-change (FC>12). The augmentation of DEFA1 abundance in patients with WNND was confirmed at the CSF, but also in serum, compared to the control individual groups. Furthermore, the DEFA1 serum level was significantly elevated in WNND patients compared to subjects diagnosed for WNF. The present study provided the first insight into the potential CSF biomarkers associated with WNV neuroinvasion. Further investigation in larger cohorts with kinetic sampling could determine the usefulness of measuring DEFA1 as diagnostic or prognostic biomarker of detrimental WNND evolution.
The cerebrospinalfluid (CSF) levels of the proapoptotic kinase R (PKR) and its phosphorylated PKR (pPKR) are increased in Alzheimer’s disease (AD), but whether CSF PKR concentrations are associated with cognitive decline in AD patients remain unknown. In this study, 41 consecutive patients with AD and 11 patients with amnestic mild cognitive impairment (aMCI) from our Memory Clinic were included. A lumbar puncture was performed during the following month of the clinical diagnosis and Mini-Mental State Examination (MMSE) evaluations were repeated every 6 months during a mean follow-up of 2 years. In AD patients, linear mixed models adjusted for age and sex were used to assess the cross-sectional and longitudinal associations between MMSE scores and baseline CSF levels of A? peptide (A? 1-42), Tau, phosphorylated Tau (p-Tau 181), PKR and pPKR. The mean (SD) MMSE at baseline was 20.5 (6.1) and MMSE scores declined over the follow-up (-0.12 point/month, standard error [SE]?=?0.03). A lower MMSE at baseline was associated with lower levels of CSF A? 1–42 and p-Tau 181/Tau ratio. pPKR level was associated with longitudinal MMSE changes over the follow-up, higher pPKR levels being related with an exacerbated cognitive deterioration. Other CSF biomarkers were not associated with MMSE changes over time. In aMCI patients, mean CSF biomarker levels were not different in patients who converted to AD from those who did not convert.These results suggest that at the time of AD diagnosis, a higher level of CSF pPKR can predict a faster rate of cognitive decline.
Streptococcus suis (SS) is an important pathogen of pigs, and it is also recognized as a zoonotic agent for humans. SS infection may result in septicemia or meningitis in the host. However, little is known about genes that contribute to the virulence process and survival within host blood or cerebrospinalfluid (CSF). Small RNAs (sRNA) have emerged as key regulators of virulence in several bacteria, but they have not been investigated in SS. Here, using a differential RNA-sequencing approach and RNAs from SS strain P1/7 grown in rich medium, pig blood, or CSF, we present the SS genome-wide map of 793 transcriptional start sites and 370 operons. In addition to identifying 29 sRNAs, we show that five sRNA deletion mutants attenuate SS virulence in a zebrafish infection model. Homology searches revealed that 10 sRNAs were predicted to be present in other pathogenic Streptococcus species. Compared with wild-type strain P1/7, sRNAs rss03, rss05, and rss06 deletion mutants were significantly more sensitive to killing by pig blood. It is possible that rss06 contributes to SS virulence by indirectly activating expression of SSU0308, a virulence gene encoding a zinc-binding lipoprotein. In blood, genes involved in the synthesis of capsular polysaccharide (CPS) and subversion of host defenses were up-regulated. In contrast, in CSF, genes for CPS synthesis were down-regulated. Our study is the first analysis of SS sRNAs involved in virulence and has both improved our understanding of SS pathogenesis and increased the number of sRNAs known to play definitive roles in bacterial virulence. PMID:24759092
We report a case of meningitis due to Salmonella typhimurium in a four-month-old female infant. The child was brought to the pediatric emergency department with complaints of fever, cold, and generalized convulsion. On examination, the child was febrile and was having seizures. The anterior fontanelle was not bulging. Lumbar puncture was done and Salmonella typhimurium was isolated from cerebrospinalfluid. Initially the infant improved clinically with appropriate management, but had a fatal outcome due to nosocomial pneumonia.
We report a case of meningitis due to Salmonella typhimurium in a four-month-old female infant. The child was brought to the pediatric emergency department with complaints of fever, cold, and generalized convulsion. On examination, the child was febrile and was having seizures. The anterior fontanelle was not bulging. Lumbar puncture was done and Salmonella typhimurium was isolated from cerebrospinalfluid. Initially the infant improved clinically with appropriate management, but had a fatal outcome due to nosocomial pneumonia. PMID:24501496
A 58-year-old man from Surinam was referred because of nausea, vomiting, weight loss, ascites and an altered mental state. Tuberculous meningitis was suspected upon examination of the cerebrospinalfluid and antituberculous treatment was initiated. However, the patient did not recover but developed haemiplegia with recurrent aspiration pneumonias. This case illustrates that empiric antituberculous treatment is warranted upon clinical suspicion, since no fast, sensitive diagnostic tests are available to date. PMID:22907858
Sonneveld, Myrthe Elisabeth; Zinkstok, S M; Nellen, F J B; Holleboom, Adriaan G
Central catecholamine deficiency characterizes ?-synucleinopathies such as Parkinson’s disease. We hypothesized that cerebrospinalfluid levels of neuronal metabolites of catecholamines provide neurochemical biomarkers of these disorders. To test this hypothesis we measured cerebrospinalfluid levels of catechols including dopamine, norepinephrine and their main respective neuronal metabolites dihydroxyphenylacetic acid and dihydroxyphenylglycol in Parkinson’s disease and two other synucleinopathies, multiple system atrophy and pure autonomic failure. Cerebrospinalfluid catechols were assayed in 146 subjects—108 synucleinopathy patients (34 Parkinson’s disease, 54 multiple system atrophy, 20 pure autonomic failure) and 38 controls. In 14 patients cerebrospinalfluid was obtained before or within 2 years after the onset of parkinsonism. The Parkinson’s disease, multiple system atrophy and pure autonomic failure groups all had lower cerebrospinalfluid dihydroxyphenylacetic acid [0.86?±?0.09 (SEM), 1.00?±?0.09, 1.32?±?0.12?nmol/l] than controls (2.15?±?0.18?nmol/l; P?0.0001; P?0.0001; P?=?0.0002). Dihydroxyphenylglycol was also lower in the three synucleinopathies (8.82?±?0.44, 7.75?±?0.42, 5.82?±?0.65?nmol/l) than controls (11.0?±?0.62?nmol/l; P?=?0.009, P?0.0001, P?0.0001). Dihydroxyphenylacetic acid was lower and dihydroxyphenylglycol higher in Parkinson’s disease than in pure autonomic failure. Dihydroxyphenylacetic acid was 100% sensitive at 89% specificity in separating patients with recent onset of parkinsonism from controls but was of no value in differentiating Parkinson’s disease from multiple system atrophy. Synucleinopathies feature cerebrospinalfluid neurochemical evidence for central dopamine and norepinephrine deficiency. Parkinson’s disease and pure autonomic failure involve differential dopaminergic versus noradrenergic lesions. Cerebrospinalfluid dihydroxyphenylacetic acid seems to provide a sensitive means to identify even early Parkinson’s disease.
Capillary zone electrophoresis and high-resolution agarose gel electrophoresis were compared to detect protein components in serum and cerebrospinalfluid of patients. Both electrophoretic methods proved to be useful for detection of protein abnormalities (e.g., mono- and oligoclonal bands) in biological fluids, but capillary electrophoresis offered several important advantages, such as sample application without preliminary concentration, lack of staining procedures, and
Mariella Ivanova; Elena Tzvetanova; Veska Jetcheva; Ferenc Kilár
Alterations in inner ear fluid pressure and cochlear microphonics (CM) associated with increased cerebrospinalfluid (CSF) pressure were studied in the guinea pig. Hydrostatic pressure in the endolymph and perilymph of the cochlea were measured by use of a servo-controlled micropipet system. Endolymphatic and perilymphatic pressure increased in a linear manner with little or no time lag following pressure increases
Streptococcus pneumoniae is a common cause of forms of bacterial meningitis that have a high mortality rate and cause long-term neurologic sequelae. We evaluated the effects of an indoleamine 2,3-dioxygenase (IDO) inhibitor on proinflammatory mediators and memory in Wistar rats subjected to pneumococcal meningitis. The animals were divided into 4 groups: sham, sham treated with IDO inhibitor, meningitis, and meningitis treated with IDO inhibitor. During the first experiment, the animals were killed 24 hours later, and the hippocampus was isolated for the analysis of tumor necrosis factor (TNF)-?, interleukin (IL)-4, IL-6, IL-10, and cytokine-induced neutrophil chemoattractant 1 (CINC-1) levels. The survival rate was 56.296% in the meningitis group and 29.616% in the meningitis group with IDO inhibitor. In the control group, we found a mean of 14.29 white blood cells/mL cerebrospinalfluid, whereas the mean was 80.00 white blood cells/mL cerebrospinalfluid in the sham IDO inhibitor group, 1167.00 white blood cells/mL cerebrospinalfluid in the meningitis group, and 286.70 white blood cells/mL cerebrospinalfluid in the meningitis IDO inhibitor group. In the meningitis group with IDO inhibitor, the levels of TNF-? and CINC-1 were reduced. In the second experiment, animals were subjected to a behavioral task and cytokine analysis 10 days after meningitis induction. In the meningitis group, there was an impairment of aversive memory. However, in the meningitis group that received adjuvant treatment with the IDO inhibitor, animals demonstrated preservation of aversive memory. These findings showed dual effects of the IDO inhibitor on a pneumococcal meningitis animal model because the inhibitor impaired survival but also produced beneficial effects, including anti-inflammatory activity and neuroprotection against the latter behavioral deficits. PMID:23994082
Barichello, Tatiana; Generoso, Jaqueline S; Simões, Lutiana R; Elias, Samuel G; Tashiro, Michael H; Dominguini, Diogo; Comim, Clarissa M; Vilela, Márcia Carvalho; Teixeira, Antonio Lucio; Quevedo, João
We report a case of meningitis due to Lactobacillus rhamnosus in a child undergoing allogeneic hematopoietic stem cell transplantation for acute leukemia. Four episodes of bacteremia involving strains with pulsotypes identical to that of the cerebrospinalfluid isolate preceded meningitis. After several courses of clindamycin, no relapse occurred during the patient follow-up.
A 1 year old Caucasian male born with an omphalocoele, malrotation of the large bowel, and Ladd's bands developed an E. coli wound infection and subsequent meningitis-ventriculitis which responded to antibiotic therapy. Aqueductal stenosis and obstructive hydrocephalus initially was treated with a ventriculoperitoneal shunt. After a routine diphtheria-pertussis-tetanus immunization, the child developed a CSF ascites which resolved following a ventriculoatrial shunt. Images
ARTCEREB, an irrigation and perfusion solution (Artcereb), is a preparation intended for the irrigation and perfusion of the cerebral ventricles, and it is therefore important to evaluate its effects on cerebrospinalfluid (CSF) and on the surrounding cerebrospinal parenchyma. To confirm the kinetics of the perfusion fluid component, we performed whole body autoradiography and examined glucose balance during ventriculocisternal perfusion with (14)C-glucose labeled Artcereb in the rat model, which simulates ventricular irrigation or ventriculocisternal perfusion in clinical neurosurgery. We also performed ventriculocisternal perfusion with Artcereb, lactated Ringer's solution, or normal saline, and observed the effect of these solutions on animal condition and on brain tissue morphology. In the kinetic study, diffusion of (14)C-glucose from the perfused Artcereb to the cerebrospinal tissue was seen on whole body autoradiography, and almost 90% of the glucose in the perfusion fluid was distributed to the cerebrospinal tissue and the systemic circulation. These data indicated that the perfusion fluid interacted actively with the CSF, surrounding parenchyma and the systemic circulation, and suggested that the formation of perfusion fluid affected CSF composition and cerebrospinal tissue functions. Animals perfused with normal saline were associated with serious symptoms including tonic convulsions and death, and exhibited neuronal death in the cerebrum. However, these severe changes were not observed in animals perfused with Artcereb or lactated Ringer's solution. We therefore propose that during neurosurgery, it is extremely important to use a physiological solution like Artcereb which closely resembles normal human CSF, in order to maintain cerebrospinal function and to alleviate postoperative adverse events. PMID:19797859
Enteroviruses (EVs) constitute the most common cause of aseptic meningitis in both children and adults. Molecular techniques have now been recognized as the reference standard for the diagnosis of EV infections, and the rapidity of the molecular diagnosis of EV meningitis has been shown to be a determining factor in the management of patients. The rapid documentation of EV RNA in cerebrospinalfluid (CSF) is key to adapting patient management and the therapeutic regimen. To shorten the time needed for virological documentation, we implemented EV RNA detection in two point-of-care (POC) laboratories. Here, we present the results of the POC detection of EV RNA with the Xpert EV kit on the GeneXpert integrated system, and a comparison with the real-time RT-PCR (rtRT-PCR) assay routinely used in the core virology laboratory. From January to September 2009, a total of 310 CSF samples were tested. The rtRT-PCR gave 81 positive, 225 negative and four 'indeterminate' results. POC results were concordant in 81.6% (253/310). Most of the discrepancies consisted of 'indeterminate' results at the POC level (16%). Calculated performances (excluding the indeterminate results) of the Xpert EV kit on the GeneXpert system in POC settings were 100%, 98.9%, 97.6% and 100% for Sensibility, Specificity, positive predictive value and negative predictive value, respectively. Taken together, these results indicate that the implementation of POC detection of EV RNA can provide robust results in <4 h, and may have a significant impact on patient management, therapeutic attitude, and hospitalization costs. PMID:21848972
Ninove, L; Nougairede, A; Gazin, C; Zandotti, C; Drancourt, M; de Lamballerie, X; Charrel, R N
Cerebrospinalfluid leaks of the temporal bone are rare, often occult, and sometimes challenging to localize and repair. This is a retrospective study of eight patients with spontaneous cerebrospinalfluid leak and six patients with cerebrospinalfluid leak or encephalocele discovered during chronic ear surgery who were treated in a tertiary medical center over a 5-year period. All received preoperative temporal bone computed tomography, and six also underwent magnetic resonance imaging, one computed tomography cisternography, and one radionuclide cisternography. All patients initially underwent a transmastoid surgical approach. Additional exposure was necessary in three patients; two underwent middle fossa craniotomy and another required minicraniotomy. Primary surgical repair was successful in six of the eight patients with spontaneous leaks and in all six chronic ear patients. Both recurrences required intradural middle fossa repair. An individualized approach should be taken for repair of temporal bone cerebrospinalfluid leaks. In this series, most were successfully repaired in a single stage using a transmastoid or combined approach. The transmastoid approach provides information about the precise size and location of the dural defect. A primary transcranial approach is needed for defects that are multiple, located in the petrous apex, and in revision cases. PMID:21311618
Pelosi, Stanley; Bederson, Joshua B; Smouha, Eric E
Background: Adrenomedullin (AM), a vasorelaxant peptide, is secreted into the cerebrospinalfluid (CSF) from the choroid plexus and can exert natriuretic effects in the kidney. CSF AM concentration is elevated 7–10 days after the onset of aneurysmal subarachnoid hemorrhage (SAH). The aim of the present study was to determine whether CSF AM concentrations correlate with hyponatremia and delayed ischemic neurological
Epidermal growth factor (EGF), a mitogenic peptide, is widely distributed within the brain and endocrine cells of the gastro-intestinal tract. Using EGF radioreceptor assay, the EGF level was measured in lumbar cerebrospinalfluid from five patients with amyotrophic lateral scerlosis (ALS) and seven patients with intervertebral disc disease as a control group. The patients with ALS showed reduced EGF levels
D. Cie?lak; J. Szulc-Kuberska; H. Stepiefi; A. Klimek
The recent studies indicating the transiently enhanced expression of excitatory amino acid receptors in hypoxia vulnerable brain regions and the elevated concentration of aspartate and glutamate in cerebrospinalfluid of asphyxiated newborns strongly suggest the role of excitatory amino acids in hypoxic ischemic brain damage in the developing human brain. In this study, we compared the concentrations of glutamate, aspartate,
K?v?lc?m Gücüyener; Y?ld?z Atalay; Yusuf Ziya Aral; Alev Hasano?lu; Canan Türky?lmaz; Gürsel Bibero?lu
Background: Inositol monophosphatase (IMPase) is a key enzyme in the regulation of the activity of the phosphatidyl inositol (PI) signaling pathway. This enzyme is also found in the cerebrospinalfluid (CSF), where it may prove useful as a marker of dysfunctional PI signal transduction.Methods: IMPase activity was measured in lumbar CSF of depressed and neuroleptic-treated schizophrenic patients. In addition, and
Major depression and posttraumatic stress disorder (PTSD) are often comorbid, resulting in more impairment compared than with either diagnosis alone. Both major depression and PTSD are thought to be associated with monoamine transmitter abnormalities. This study compared clinical features and cerebrospinalfluid (CSF) monoamine metabolites in drug-free depressed subjects with a current major depressive episode (MDE) without comorbid PTSD, subjects
Leo Sher; Maria A. Oquendo; Shuhua Li; Ainsley K. Burke; Michael F. Grunebaum; Gil Zalsman; Yung-yu Huang; J. John Mann
DETERMINATIONS of alpha-ketoglutaric acid and pyruvic acid in blood, cerebrospinalfluid and urine have been carried out using 2,4-dinitrophenylhydrazone method.1 The keto-acid hydrazones were separated, either by paper electrophoresis or by paper chromatography.
BACKGROUND: The clinical response to spinal anesthesia is influenced by lumbosa- cral cerebrospinalfluid (CSF) volume, which is highly variable among patients. METHODS: Lumbosacral magnetic resonance images were obtained in 71 patients using a long echo time (TE 198 msec), fast spin echo sequence with fat suppression. Three-dimensional images were created and lumbosacral CSF volume was estimated using a threshold-based
John T. Sullivan; Sharon Grouper; Matthew T. Walker; Todd B. Parrish; Robert J. McCarthy; Cynthia A. Wong
Background: Polymerase chain reaction (PCR) is used to detect viruses in the cerebrospinalfluid (CSF) of patients with neurological disease. However, data to assist its use or interpretation are limited.Objective: We investigated factors possibly influencing viral detection in CSF by PCR, which will also help clinicians interpret positive and negative results.Methods: CSF from patients with was tested for human herpesviruses
N W S Davies; L J Brown; J Gonde; D Irish; R O Robinson; A V Swan; J Banatvala; R S Howard; M K Sharief; P Muir
The use of nucleic acid (NA) amplification techniques has transformed the diagnosis of viral infections of the central nervous system (CNS). Because of their enhanced sensitivity, these methods enable detection of even low amounts of viral genomes in cerebrospinalfluid. Following more than 10 years of experience, the polymerase chain reaction or other NA-based amplification techniques are nowadays performed in
PURPOSE: To analyze the characteristics of normal cerebrospinalfluid (CSF) flow waveforms and to relate them to the arterial input and venous output flow waveforms in healthy volunteers. METHODS: Cine phase-contrast MR was obtained in 17 volunteers. The temporal velocity infor- mation from the cervical pericord CSF spaces, basal cisterns, and aqueduct, as well as the internal carotid and vertebral
Rafeeque A. Bhadelia; Andrew R. Bogdan; Samuel M. Wolpert
Central nervous system (CNS) infection is a constant feature of systemic HIV infection with a clinical spectrum that ranges from chronic asymptomatic infection to severe cognitive and motor dysfunction. Analysis of cerebrospinalfluid (CSF) has played an important part in defining the character of this evolving infection and response to treatment. To further characterize CNS HIV infection and its effects,
Thomas E. Angel; Jon M. Jacobs; Serena S. Spudich; Marina A. Gritsenko; Dietmar Fuchs; Teri Liegler; Henrik Zetterberg; David G. Camp; Richard W. Price; Richard D. Smith
Piroxantrone is an anthrapyrazole derivative with broad anti-tumor activityin vitro and less cardiac toxicity than the anthracyclines. The metabolic pathways and central nervous system penetration of piroxantrone have not been determined. In this study we examined the pharmacokinetic behavior of piroxantrone in plasma and cerebrospinalfluid in a non-human primate model. In addition, a urinary metabolite of piroxantrone was isolated
Stacey L. Berg; Frank M. Balis; Karen S. Godwin; David G. Poplack
Accurate analysis of cerebrospinalfluid (CSF) provides a wide range of information about the neurological health of the patient. CSF can be withdrawn from either of two cisterns in dogs and cats using relatively safe techniques. Once CSF has been collected it must be analysed immediately and methodically. Evaluation should consist of macroscopic, quantitative and microscopic analyses. As part of
In 74 patients with different attack rates and patterns mean levels of hexamidine in the blood plasma and cerebrospinalfluid were 15.9 micrograms/ml and 7.86 micrograms/ml, respectively, the former almost twice as high as the latter. Both were found to correlate with the drug daily doses and other anticonvulsants administration. PMID:3188751
Motion of the cerebrospinalfluid (CSF) in and around the brain and spinal cord was examined in healthy subjects and in a number of patients with abnormalities of the CSF circulation. The pulsatile motion of the CSF was determined by spin echo phase (velocity) imaging, sometimes in combination with gradient echo phase contrast cine. Differences in flow patterns across CSF
Schizophrenia is a serious brain disease of uncertain etiology. A role for retroviruses in the etiopathogenesis of some cases of schizophrenia has been postulated on the basis of clinical and epidemiological observations. We found sequences homologous to retroviral pol genes in the cell-free cerebrospinalfluids (CSFs) of 10 of 35 (29%) individuals with recent-onset schizophrenia or schizoaffective disorder. Retroviral sequences
Håkan Karlsson; Silke Bachmann; Johannes Schroder; Justin McArthur; E. Fuller Torrey; Robert H. Yolken
The concentration of lead in blood, serum, cerebrospinalfluid, and urine was measured in patients with neurological disease and in control subjects including cases of plumbism. A plot of blood lead versus serum lead resembles the familiar curves of blood lead versus either free erythrocyte porphyrin or urinary delta-aminolaevulinic acid in that serum lead is constant up to a blood
Adults with intestinal malabsorption due to celiac disease show reduced central serotonin metabolism, probably induced by a lack of essential dietary factors. Investigating a role proposed for vitamin B6 deficiency, a regular finding in untreated celiacs, the present study yields no support for the hypothesis that direct inhibition at the decarboxylation step by vitamin B6 deficiency accounts for low central serotonin turnover in adult celiacs: 11 untreated patients showing reduced 5-HIAA in the cerebrospinalfluid (71+/- 26.8 pmol/ml) had a significantly higher concentration of the metabolically active B6 vitamer pyridoxal 5'-phosphate in lumbar cerebrospinalfluid (0.06 +/- 0.34 ng/ml) than controls (0.24 +/- 0.07 ng/ml) (p less than 0.01). Cerebrospinalfluid tryptophan, precursor of serotonin, was normal (2035 %/- 649 pmol/ml). Raised pyridoxal 5'-phosphate in the cerebrospinalfluid in untreated celiac disease is an unexpected finding. Possibly it is secondary to the diminished central monamine metabolism in these patients, but further studies are needed bearing in mind that mental depression is a major cause for disability in adult celiac disease. PMID:6182788
Hallert, C; Allenmark, S; Larsson-Cohn, U; Sedvall, G
Double ring formation in single radial immunodiffusion for light chains of type kappa and not for light chains of type lambda was observed in cerebrospinalfluid in 24 out of 42 patients with multiple sclerosis, 1 patient with cerebral cysticercosis, 1 of 3 patients with neurosyphilis and 1 patient with spastic paraparesis of unknown eitology. Double ring formation was not
The effect of intracerebroventricular (lateral ventricle) administration of arginine8-vasopressin (AVP) on the concentration of beta-endorphin immunoreactivity in the cerebrospinalfluid obtained from the cisterna magna was studied in rats. A decrease was observed 5 min following injection of 0.9 fmol AVP. No statistically significant changes were found 5 min after intracerebroventricular treatment of rats with 0.09 or 9 fmol. The decrease induced by 0.9 fmol AVP was of short duration and was found 5 min after treatment but not 10 and 20 min. Desglycinamide9-AVP (0.97 fmol), [pGlu4, Cyt6]-AVP-(4-9) (1.44 fmol), N alpha-acetyl-AVP (0.88 fmol), lysine8-vasopressin (0.94 fmol) and oxytocin (1 fmol) when intracerebroventricularly injected did not affect the levels of beta-endorphin immunoreactivity in the cerebrospinalfluid 5 min later. This suggests that the intact AVP-(1-9) molecule is required for this effect. Intracerebroventricular pretreatment of rats with the vasopressin V1-receptor antagonist d(CH2)5Tyr(Me)AVP (8.63 fmol) completely blocked the effect of AVP (0.9 fmol). In order to investigate further the underlying mechanism, the effect of AVP on the disappearance from the cerebrospinalfluid of exogenously applied beta-endorphin was determined. Following intracerebroventricular injection of 1.46 pmol camel beta-endorphin-(1-31), the beta-endorphin immunoreactivity levels in the cisternal cerebrospinalfluid increased rapidly, and reached peak values at 10 min. The disappearance of beta-endorphin immunoreactivity from the cerebrospinalfluid then followed a biphasic pattern with calculated half-lives of 28 and 131 min for the initial and the terminal phase, respectively. Treatment of rats with AVP (0.9 fmol; icv) during either phase (10, 30, 55 min following intracerebroventricular administration of 1.46 pmol beta-endorphin-(1-31)) significantly enhanced the disappearance of beta-endorphin immunoreactivity from the cerebrospinalfluid. The data suggest that vasopressin plays a role in the regulation of beta-endorphin levels in the cerebrospinalfluid by modulating clearance mechanisms via V1-receptors in the brain. PMID:2138399
Sweep, C G; Boomkamp, M D; Barna, I; Logtenberg, A W; Wiegant, V M
We studied a variety of patients with measles virus infection by using avidity testing for measles virus-specific immunoglobulin G (IgG) in serum and cerebrospinalfluid samples. For the avidity testing, an Enzygnost measles IgG enzyme-linked immunosorbent assay kit was used with an 8 M urea denaturing method. With this method, low-avidity IgG (acute primary infection, avidity of < 30% within 15 days of the onset of rash) and high-avidity IgG (subacute sclerosing panencephalitis, avidity of > 75%) could be clearly distinguished by using serum samples. One patient, who developed a typical course of measles despite a previous vaccination, showed a positive IgM response with an initial low titer of measles virus-specific IgG of low avidity, but a later sample revealed a high titer of IgG of intermediate (40%) avidity, suggesting previous immunological priming. Two patients with breakthrough infection (secondary vaccine failure), both having central nervous system involvement, showed a positive IgM response with initial high titers of serum IgG of high avidity. In addition, one of the patients had a detectable level of measles-specific IgG in cerebrospinalfluid. In this patient, the avidity of both serum and cerebrospinalfluid IgG decreased during the short follow-up period. This phenomenon has never before been reported. In subacute sclerosing panencephalitis patients, the avidity of cerebrospinalfluid IgG was consistently lower than that of serum IgG. The difference in avidity between cerebrospinalfluid and serum IgG may be used as a direct indicator of intrathecal production of IgG. In conclusion, the avidity testing is simple to perform, reliable, and highly informative in the analysis of measles virus infection.
Narita, M; Yamada, S; Matsuzono, Y; Itakura, O; Togashi, T; Kikuta, H
Introduction CyberKnife® radiation is an effective treatment for unresectable skull base tumors because it can deliver a highly conformational dose distribution to the complex shapes of tumor extensions. There have been few reports of severe complications with this treatment. This is the first published case report to our knowledge of cerebrospinalfluid leakage induced by CyberKnife® radiotherapy. Case presentation A skull base tumor was identified on magnetic resonance imaging in a 78-year-old Asian woman with a headache in her forehead. An endoscopic transnasal tumor resection was performed; however, the tumor, invading into the cavernous sinuses and optic canal, was not completely removed. During the subtotal resection of the tumor, no cerebrospinalfluid leakage was observed. Osteosarcoma was histologically diagnosed, and CyberKnife® radiation was performed to the residual tumor considering the aggressive feature of the tumor with a molecular immunology Borstel-1 index of 15%. Five months after the treatment, magnetic resonance imaging showed definite tumor shrinkage, and the patient had been living her daily life without any troubles. After another month, the patient was transferred to our clinic because of coma with high fever, and computed tomography demonstrated severe pneumocephalus. Rhinorrhea was definitely identified on admission; therefore, emergency repair of the cerebrospinalfluid leakage was performed using an endoscope. Dural defects at the bottom of the sella turcica were identified under careful endoscopic observation and fat tissue was patched to the dural defects. Follow-up computed tomography proved complete disappearance of air from the cisterns 2 weeks after the surgery, and the patient was discharged from our hospital without any neurological deficits. Conclusion CyberKnife® radiation is one of the effective treatments for skull base tumors; however, the risk of cerebrospinalfluid leakage should be considered when tumor invasion to the dura mater is suspected. Emergency surgical treatment is required when cerebrospinalfluid leakage is induced by the radiotherapy because the leakage is not expected to be healed by palliative treatments.
A 23-year-old obese woman presented with papilledema. Computed tomography showed no intracranial mass lesions and lumbar puncture revealed an increased opening pressure, confirming the diagnosis of pseudo-tumor cerebri. Standardized echography of the optic nerves was performed immediately before and after lumbar puncture. A marked reduction of cerebrospinalfluid pressure correlated with a decrease in the subarachnoid fluid of the optic nerve sheath. PMID:2526162
A lightweight, adjustable adapter has been designed for chronic cannulation of goats (Capra hircus) which provides an accurate, safe means of sampling cerebrospinalfluid (CSF). This cisternal cannula has been used for continuous perfusion of synthetic CSF into the fourth ventricle in unanesthetized goats. This method also has been used for examining changes in ionic composition of the CSF and cerebral interstitial fluid (ISF) during physiologic adaptations to high altitude (2-5). PMID:2811283
Virological investigations of 115 children with the aseptic meningitis syndrome during 1963 resulted in the isolation of enteroviruses from cerebrospinalfluid (CSF) and/or feces of 21 of 48 children who had no association with mumps. For the third successive year, Echo 9 was the dominant enterovirus in cases of aseptic meningitis in Toronto children, but no rashes were associated with Echo 9 meningitis during 1963, in contradistinction to previous years. Mumps virus was isolated from CSF of 25 patients by inoculation of rhesus monkey kidney cultures, and rising or elevated mumps antihemagglutinin titres in paired sera from a further 33 cases provided laboratory evidence of infection with mumps virus in 58 of 67 patients with mumps meningoencephalitis. No enlargement of salivary glands was noted in 20 laboratory-proved cases of mumps meningoencephalitis. Enteroviral meningitis occurred principally during summer, but the peak of mumps meningoencephalitis occurred during late winter.
McLean, D. M.; Quantz, E. Joan; Bach, Ruth D.; Pevzner, B. Mae; Larke, R. P. B.; McNaughton, G. A.
A seminested-PCR assay, based on the amplification of the pneumococcal penicillin-binding protein 2B gene (pbp2B), was developed for the detection of penicillin-resistant and -susceptible pneumococci in cerebrospinalfluid (CSF) specimens. Species-specific primers (P5 and P6) which amplified a 682-bp conserved region of the transpeptidase-encoding region of the pbp2B gene were used. Four “resistance” primers were designed to bind to altered areas of the pbp2B gene identified in penicillin-resistant South African wild-type strains. Together with the downstream primer P6, the upstream resistance primers amplified fragments which were used to detect the presence of penicillin resistance. This system identified all 35 of the S. pneumoniae isolates evaluated, including strains of 11 different serotypes and a range of penicillin-resistant and -susceptible strains. The specificity of the assay was demonstrated by its inability to amplify DNA from other bacterial species which commonly cause meningitis. It was possible to detect pneumococcal DNA from culture-negative CSF inoculated with 2.5 pg of purified DNA or 18 CFU. Analysis of 285 CSF specimens showed that PCR detected the pneumococcus in 18 samples positive by culture, including the identification of four penicillin-resistant isolates. The positive predictive value and the negative predictive value of the assay were each 100%.
du Plessis, Mignon; Smith, Anthony M.; Klugman, Keith P.
Varicella zoster virus (VZV) like other alphaherpes viruses stays latent after its primary infection. During its reactivation, it can infect the central nervous system (CNS) causing a variety of clinical presentations. Using polymerase chain reaction (PCR) for detection of VZV DNA in cerebrospinalfluid (CSF), it is now recognized in some series as the most common causative agent of viral CNS infection. We aimed to investigate in our study the correlation between VZV viral load in the CSF and the clinical course of its infection, using quantitative real-time PCR. For this purpose, we examined 56 specimens of consecutive patients with positive CSF for VZV DNA in a qualitative test, with a clinical picture of meningitis or encephalitis collected over 10years in Rambam medical center. We found a significant correlation between VZV viral load and the severity and duration of neurological disease. We believe that using quantitative measurement of VZV DNA in the CSF, could serve as a prognostic marker which would influence treatment decisions. PMID:24666705
Persisting embryonal infundibular recess (PEIR) is a rare anomaly of the third ventricular floor. Only eight cases have been published. In this report, a case of presumably Rathke's cleft cyst associated with cerebrospinalfluid leakage caused by PEIR is described. An 81-year-old woman underwent endoscopic transsphenoidal surgery for the intra- and supra-sellar cystic lesion. Intraoperatively a hole was confirmed over the sella turcica connecting the sellar cyst and the infundibular recess. Liquorrhea did not occur throughout the procedure. A computed tomography (CT) scan obtained immediately after surgery disclosed accumulation of air in the third and lateral ventricles, in addition to the intra- and supra-sellar region. Air accumulation resolved spontaneously after bed rest for 11 days and she was discharged without neurological deficits. However, she required the second transsphenoidal surgery to repair the sellar floor because of bacterial meningitis caused by liquorrhea on the postoperative day 23. A postoperative 3-tesla magnetic resonance image revealed a deep infundibular recess connecting the sella turcica and the third ventricle, which was considered to be PEIR. To the best our knowledge, this is the first reported case describing the intraoperative findings of PEIR. PMID:24305020
We describe the use of PCR and electrospray ionization followed by mass spectrometry (PCR/ESI-MS) to evaluate “culture-negative” cerebrospinalfluid (CSF) from a 67-year-old man who developed postoperative bacterial ventriculitis following a suboccipital craniotomy for resection of an ependymoma in the 4th ventricle. CSF samples were obtained on seven occasions, beginning in the operating room at the time of insertion of a right ventriculoperitoneal shunt (VPS) and continuing until his death, 6 weeks later. During the course of the illness, two initial CSF specimens taken before the initiation of antimicrobial treatment were notable for growth of Enterococcus faecalis. Once antimicrobial treatment was initiated, all CSF cultures were negative. PCR/ESI-MS detected genetic evidence of E. faecalis in all CSF samples, but the level of detection (LOD) decreased once antimicrobial treatment was initiated. When our patient returned with symptoms of meningitis 3 days after the completion of antibiotic treatment, CSF cultures remained negative, but PCR/ESI-MS again found genetic evidence for E. faecalis at levels comparable to the pretreatment levels seen initially. This unique case and these findings suggest that determination of CSF LOD by PCR/ESI-MS may be a very sensitive indicator of persistent infection in patients on antibiotic therapy for complex CNS infections and may have relevance for treatment duration and assessment of persistent or recurrent infection at the completion of therapy.
Tsung, Andrew J.; Flier, Lisa; Martinez, Derek L.; Beam, Sarah B.; Chen, Clifford; Lowery, Kristin S.; Sampath, Rangarajan; Bonomo, Robert A.
The entry of anti-infectives into the central nervous system (CNS) depends on the compartment studied, molecular size, electric charge, lipophilicity, plasma protein binding, affinity to active transport systems at the blood-brain/blood-cerebrospinalfluid (CSF) barrier, and host factors such as meningeal inflammation and CSF flow. Since concentrations in microdialysates and abscesses are not frequently available for humans, this review focuses on drug CSF concentrations. The ideal compound to treat CNS infections is of small molecular size, is moderately lipophilic, has a low level of plasma protein binding, has a volume of distribution of around 1 liter/kg, and is not a strong ligand of an efflux pump at the blood-brain or blood-CSF barrier. When several equally active compounds are available, a drug which comes close to these physicochemical and pharmacokinetic properties should be preferred. Several anti-infectives (e.g., isoniazid, pyrazinamide, linezolid, metronidazole, fluconazole, and some fluoroquinolones) reach a CSF-to-serum ratio of the areas under the curves close to 1.0 and, therefore, are extremely valuable for the treatment of CNS infections. In many cases, however, pharmacokinetics have to be balanced against in vitro activity. Direct injection of drugs, which do not readily penetrate into the CNS, into the ventricular or lumbar CSF is indicated when other effective therapeutic options are unavailable. PMID:20930076
This study evaluated the performance of a real-time polymerase chain reaction (PCR) assay in comparison with Gram staining and culture of cerebrospinalfluid for the diagnosis of meningococcal and pneumococcal meningitis in patients with suspected bacterial meningitis. The sensitivity for detection of Neisseria meningitidis in cerebrospinalfluid was 87% (20/23) for the PCR assay, 27% (6/22) for Gram staining, and 17% (4/23) for culture. The sensitivity for detection of Streptococcus pneumoniae in cerebrospinalfluid was 100% (14/14) for the PCR assay, 62% (8/13) for Gram staining, and 36% (5/14) for culture. Therefore, we recommend that real-time PCR of cerebrospinalfluid for detection of N. meningitidis and S. pneumoniae become a part of the routine diagnostic procedure for patients with suspected bacterial meningitis. PMID:17610095
Van Gastel, E; Bruynseels, P; Verstrepen, W; Mertens, A
Background Conventional laboratory diagnosis of bacterial meningitis based on microscopy followed by culture is time-consuming and has only moderate sensitivity. Objectives The objective was to define the limit of detection (LOD), analytic specificity, and performance characteristics of a broad-based quantitative multiprobe polymerase chain reaction (PCR) assay for rapid bacterial detection and simultaneous pathogen-specific identification in patients with suspected meningitis. Methods A PCR algorithm consisting of initial broad-based detection of Eubacteriales by a universal probe, followed by pathogen identification using either pathogen-specific probes or Gram-typing probes, was employed to detect pathogens. The 16S rRNA gene, which contains both conserved and variable regions, was chosen as the target. Pathogen-specific probes were designed for Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, and Listeria monocytogenes. Gram-positive and -negative typing probes were designed based on conserved regions across all eubacteria. The LOD and time to detection were assessed by dilutional mocked-up samples. A total of 108 convenience cerebrospinalfluid (CSF) clinical samples obtained from the Johns Hopkins Hospital (JHH) microbiology laboratory were tested, and results were compared with hospital microbiologic culture reports. Results The LOD of the assay ranged from 101 to 102 colony-forming units (CFU) / mL. Pathogen-specific probes showed no cross-reactivity with other organisms. Time to detection was 3 hours. In clinical specimens, the universal probe correctly detected 16 of 22 culture-positive clinical specimens (sensitivity = 72.7%; 95% confidence interval [CI] = 49.8% to 89.3%), which were all correctly characterized by either pathogen-specific or Gram-typing probes. Adjusted sensitivity after removing probable microbiologic laboratory contaminants was 88.9% (95% CI = 65.3% to 98.6%). The universal probe was negative for 86 of 86 culture-negative specimens. Conclusions A broad-based multiprobe PCR assay demonstrated strong analytic performance characteristics. Findings from a pilot clinical study showed promise in translation to human subjects, supporting potential utility of the assay as an adjunct to traditional diagnostics for early identification of bacterial meningitis.
Typhoidal and nontyphoidal salmonella infections are common causes of gastroenteritis in the community. However, salmonella only rarely causes invasive infections like meningitis. We report a 13-day-old female neonate with signs and symptoms of meningitis whose cerebrospinalfluid (CSF) culture showed Salmonella enterica serotype Arizonae that was sensitive to ceftriaxone. She presented with fever and failure to feed for 2 days. Despite prompt treatment with ampicillin, gentamicin, and ceftriaxone, she developed communicating hydrocephalus, frequent seizures, and coma that progressed to death after 2 weeks of hospitalization. Salmonella enterica serotype Arizonae is a rare cause of human infection known to leading to meningitis symptoms similar to those caused by other salmonella species. This is the first report of it as a cause of meningitis in a child under one month of age. Therefore, it should be included in the differential diagnosis of Gram-negative bacillary meningitis in immunocompromised children, neonates, and those with contacts with reptiles.
Lakew, Wubishet; Girma, Abayneh; Triche, Elizabeth
Introduction Pantoea calida, a recently described environmental Enterobacteriaceae organism, has not yet been associated with human infection. Case presentation We report a case of postoperative meningitis caused by P. calida. After pituitary adenoma resection, a 52-year-old Caucasian woman developed febrile meningitis confirmed by cerebrospinalfluid analysis. P. calida was grown in pure culture from this fluid and was firmly identified with partial rpoB gene sequencing. She was cured by a 14-day course of meropenem. Conclusions P. calida must be added to the list of opportunistic Enterobacteriaceae pathogens responsible for postsurgical meningitis. It is easily identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
Bacterial meningitis is relatively common, can progress rapidly, and can result in death or permanent debilitation. This infection justifiably elicits strong emotional reactions and, hopefully, immediate medical intervention. This review is a brief presentation of the pathogenesis of bacterial meningitis and a review of current knowledge, literature, and recommendations on the subject of laboratory diagnosis of bacterial meningitis. Those who work in clinical microbiology laboratories should be familiar with the tests used in detecting bacteria and bacterial antigens in cerebrospinalfluid (CSF) and should always have the utmost appreciation for the fact that results of such tests must always be reported immediately. Academic and practical aspects of the laboratory diagnosis of bacterial meningitis presented in this review include the following: anatomy of the meninges; pathogenesis; changes in the composition of CSF; etiological agents; processing CSF; microscopic examination of CSF; culturing CSF; methods of detecting bacterial antigens and bacterial components in CSF (counter-immunoelectrophoresis, coagglutination, latex agglutination, enzyme-linked immunosorbent assay, Limulus amebocyte lysate assay, and gas-liquid chromatography); use of the polymerase chain reaction; and practical considerations for testing CSF for bacterial antigens.
Hydrocephalus is a medical condition characterized by enlargement of cerebral ventricles due to abnormal cerebrospinalfluid accumulation. Hydrocephalic women with cerebrospinalfluid (CSF) shunts are now surviving to reproductive age, but still there are doubts regarding the mode of delivery, analgesia and anesthesia. Postpartal complications are more frequently described in deliveries ended by cesarean section than in spontaneous vaginal deliveries. We present a case of labor in the 32-year old woman, with congenital hydrocephalus and a preexisting ventriculoperitoneal (VP) shunt. After thorough review of current literature, we came to conclusion that without absolute neurosurgical indication or acute development of listed symptoms (headaches, irritability, light sensitivity, hyperesthesia nausea, vomiting, vertigo, migraines, seizures, weakness in the arms or legs, strabismus and double vision) the best way to finish the pregnancy of woman with VP shunt is spontaneous vaginal delivery with the use of epidural analgesia, mediolateral episiotomy and vacuum extraction. PMID:24611354
The purpose of this retrospective study is to determine whether there is a correlation among overweight, gender and the risk of development of spontaneous cerebrospinalfluid (CSF) rhinorrhoea. The clinical data of eight patients diagnosed with spontaneous cerebrospinalfluid rhinorrhoea who had been treated at our tertiary referral centre between 1998 and 2007 were assessed. Demographically, seven patients were female and one male with ages ranging from 14 to 53 years with a mean age of 43.6 years. This observation revealed that all patients were overweight with a mean body mass index (BMI) of 32.5 kg/m2. This study suggests that there is a trend of increasing BMI to the risk of developing a spontaneous CSF rhinorrhoea. PMID:18705467
Several neuropeptide FF (NPFF)-related peptides, known as modulators of the opioid system, have been previously characterized in bovine and rodent brain. Reverse-phase high pressure liquid chromatography (HPLC) fractions of a human with normal pressure hydrocephalus cerebrospinalfluid (CSF), co-migrating with NPFF-related synthetic peptides, were characterized by capillary HPLC coupled on-line to nanospray ion trap tandem mass spectrometry. Two peptides present
Odile Burlet-Schiltz; Honoré Mazarguil; Jean-Christophe Sol; Patrick Chaynes; Bernard Monsarrat; Jean-Marie Zajac; Anne Roussin
The objective of this study was to determine the role of cerebral nitric oxide and its powerful oxidant peroxynitrite following mild birth asphyxia. The cerebrospinalfluid levels of nitric oxide and 3-nitrotyrosine as a marker for peroxynitrite are measured in neonates with mild hypoxic-ischemic encephalopathy. Based on the classification of Sarnat and Sarnat, term neonates with mild hypoxic-ischemic encephalopathy and
Secondary hydrocephalus communicans after traumatic upper cervical spine injuries with leakage of cerebrospinalfluid is a rare and hardly described complication. A case of a 75-year-old woman sustained a type II dens axis without other injuries, especially without evidence of a hydrocephalus in the primary CT scan. Dorsal atlanto-axial fusion was performed. Postoperative drainage was prolonged and positive for ?2-transferrin.
Ladislav Mica; Valentin Neuhaus; Enrico Pöschmann; Dilek Könü-Leblebicioglu; Urs Schwarz; Guido A Wanner; Clément ML Werner; Hans-Peter Simmen
SUMMARY: This retrospective chart review describes the clinical features, pathogens, and outcomes of 46 patients with cerebrospinalfluid (CSF) shunt infections collected over 16 years. The overall CSF shunt infection rate was 2.1%, broken down into 1.7 and 9.3% in adult and pediatric groups, respectively. Fever and progressive consciousness disturbance were the most prominent clinical features in the adult patient
A sensitive and simple high-performance liquid chromatographic (HPLC) assay was developed for the quantification of resiniferatoxin (RTX) in canine cerebrospinalfluid (CSF). A reversed-phase C18 column and acetonitrile in 0.02 M NaH2PO4 as mobile phase provided satisfactory resolution for RTX analysis. Direct HPLC analysis of the CSF samples without sample extraction or preparation improves the accuracy and detection limits of
Andrew J Mannes; Dorothy Cimino Brown; Sandra Z Perkowski; Jason Keller; Robert M Caudle; Michael J Iadarola; Qing C Meng
\\u000a Detection of cerebrospinalfluid (CSF) biomarkers is a major challenge for laboratories involved in neurological disorder\\u000a diagnostics and the long list of putative markers now available reflects the enormous efforts and the relevance of CSF in\\u000a neurology. The result of these intensive studies on CSF is that specific biomarkers are included as supportive criteria for\\u000a neurodegenerative disorder diagnosis. The diagnostic
Gianluigi Zanusso; Michele Fiorini; Pier Giorgio Righetti; Salvatore Monaco
Immunoprecipitation (IP) combined with matrix-assisted laser desorption ionization (MALDI) time of flight (Tof) mass spectrometry has been used to develop quantitative assays for amyloid-b (Ab) peptides in cerebrospinalfluid (CSF). Inclusion of 15N labelled standard peptides allows for absolute quantification of multiple Ab isoforms in individual samples. Characterization of variability associated with all steps of the assay indicated that the
Valentina Gelfanova; Richard E. Higgs; Robert A. Dean; David M. Holtzman; Martin R. Farlow; Eric R. Siemers; Amechand Boodhoo; Yue-Wei Qian; Xiaohua He; Zhaoyan Jin; Deborah L. Fisher; Karen L. Cox; John E. Hale
A simple, ion-pair high-performance liquid chromatographic method has been developed and validated for the quantitative determination of the HIV protease inhibitor ritonavir in human plasma, cerebrospinalfluid and saliva. Sample pretreatment consisted of precipitation of proteins with acetonitrile prior to high-performance liquid chromatography with ultraviolet detection at 239 nm. The method has been validated over the range of 50 ng\\/ml
Richard M. W Hoetelmans; Marjolijn van Essenberg; Monique Profijt; Pieter L Meenhorst; Jan W Mulder; Jos H Beijnen
The spread of cancer into the central nervous system is a serious problem leading to neurological symptoms and rapid mortality.\\u000a The current tools available for detecting the spread of cancer into the cerebrospinalfluid (CSF) are cytology, neurologic\\u000a examination, and neuroimaging. All three of these methods can be applied in concert to reach a diagnosis, but they all suffer\\u000a from
Organic acids in cerebrospinalfluid (CSF) are potential diagnostic markers for neurological diseases and metabolic disorders.\\u000a A capillary electrophoretic (CE) method for the direct analysis, i.e., without any sample preparation, of six organic acids\\u000a in CSF was developed. A capillary coating consisting of a triple layer of charged polymers (polybrene-dextran sulfate-polybrene)\\u000a was used in combination with a negative separation voltage,
Rawi Ramautar; Govert W. Somsen; Gerhardus J. de Jong
Central nervous system (CNS) diseases often induce changes in the protein composition of the cerebrospinalfluid (CSF) as\\u000a this liquid bathes the brain and collects its secreted products. The detection and monitoring of such pathology-related changes\\u000a can be exploited for their relation to tumor growth in the brain. The potential of using differential proteomic profiling\\u000a in CNS malignancies to identify
BackgroundNeurologic Post Treatment Lyme disease (nPTLS) and Chronic Fatigue (CFS) are syndromes of unknown etiology. They share features of fatigue and cognitive dysfunction, making it difficult to differentiate them. Unresolved is whether nPTLS is a subset of CFS.Methods and Principal FindingsPooled cerebrospinalfluid (CSF) samples from nPTLS patients, CFS patients, and healthy volunteers were comprehensively analyzed using high-resolution mass spectrometry
Steven E. Schutzer; Thomas E. Angel; Tao Liu; Athena A. Schepmoes; Therese R. Clauss; Joshua N. Adkins; David G. Camp; Bart K. Holland; Jonas Bergquist; Patricia K. Coyle; Richard D. Smith; Brian A. Fallon; Benjamin H. Natelson; Howard Gendelman
Measurements of the activities of lysosomal enzymes in cerebrospinalfluid have recently been proposed as putative biomarkers for Parkinson's disease and other synucleinopathies. To define the operating procedures useful for ensuring the reliability of these measurements, we analyzed several pre-analytical factors that may influence the activity of ?-glucocerebrosidase, ?-mannosidase, ?-mannosidase, ?-galactosidase, ?-fucosidase, ?-hexosaminidase, cathepsin D and cathepsin E in cerebrospinalfluid. Lysosomal enzyme activities were measured by well-established fluorimetric assays in a consecutive series of patients (n?=?28) with different neurological conditions, including Parkinson's disease. The precision, pre-storage and storage conditions, and freeze/thaw cycles were evaluated. All of the assays showed within- and between-run variabilities below 10%. At ?20°C, only cathepsin D was stable up to 40 weeks. At ?80°C, the cathepsin D, cathepsin E, and ?-mannosidase activities did not change significantly up to 40 weeks, while ?-glucocerebrosidase activity was stable up to 32 weeks. The ?-galactosidase and ?-fucosidase activities significantly increased (+54.9±38.08% after 4 weeks and +88.94±36.19% after 16 weeks, respectively). Up to four freeze/thaw cycles did not significantly affect the activities of cathepsins D and E. The ?-glucocerebrosidase activity showed a slight decrease (?14.6%) after two freeze/thaw cycles. The measurement of lysosomal enzyme activities in cerebrospinalfluid is reliable and reproducible if pre-analytical factors are accurately taken into consideration. Therefore, the analytical recommendations that ensue from this study may contribute to the establishment of actual values for the activities of cerebrospinalfluid lysosomal enzymes as putative biomarkers for Parkinson's disease and other neurodegenerative disorders.
Background Osmotherapy has been the cornerstone in the management of patients with elevated intracranial pressure (ICP) following traumatic\\u000a brain injury (TBI). Several studies have demonstrated that hypertonic saline (HTS) is a safe and effective osmotherapy agent.\\u000a This study evaluated the effectiveness of HTS in reducing intracranial hypertension in the presence of a wide range of serum\\u000a and cerebrospinalfluid (CSF) osmolalities.
Eduardo Paredes-Andrade; Sarah B. Rockswold; Rick M. Odland; Gaylan L. Rockswold
CINE phase-contrast MRI (CINE-MRI) was used to measure cerebrospinalfluid (CSF) velocities and flow rates in the brain of\\u000a six normal subjects and five patients with communicating hydrocephalus. Mathematical brain models were created using the MRI\\u000a images of normal subjects and hydrocephalic patients. In our model, the effect of pulsatile vascular expansion is responsible\\u000a for pulsatile CSF flow between the
Andreas A. Linninger; Brian Sweetman; Richard Penn
Hepatologists assay liver enzymes and cardiologists structural heart proteins in serum to diagnose and monitor their patients. This way of thinking has not quite made it into the memory clinics yet, in spite of the availability of validated cerebrospinalfluid biomarkers for key pathological events in the brain in neurodegeneration. Here, we argue that a spinal tap should be considered in all patients who seek medical advice for memory problems and list the highly relevant clinical questions CSF analyses can address.
Zetterberg, Henrik; Mattsson, Niklas; Blennow, Kaj
To evaluate cellular immune activation in opsoclonus-myoclonus syndrome, we measured the inflammatory marker neopterin in the cerebrospinalfluid of 16 children with opsoclonus-myoclonus and neuroblastoma, 24 children with opsoclonus-myoclonus but no tumor, and 19 age-matched controls. The mean concentration in opsoclonus-myoclonus was 2.3-fold higher than in controls (P = .008). Neopterin was greatly elevated in four of the most neurologically
Michael R. Pranzatelli; Keith Hyland; Elizabeth D. Tate; Lauren A. Arnold; Tyler J. Allison; Gamini S. Soori
Objective: Triflusal has been shown to exert neuroprotective effects by downregulating molecules considered responsible for the development of Alzhei- mer's disease (AD). The aim of this study was to develop a population pharmacokinetic model to characterize plasma and cerebrospinalfluid (CSF) pharmacokinetics of the main active metabolite of triflusal—HTB (2-hy- droxy-4-trifluoro-methylbenzoic acid)—in healthy vol- unteers. Methods: Data from two studies
M. Valle; M. J. Barbanoj; A. Donner; I. Izquierdo; U. Herranz; N. Klein; H. G. Eichler; M. Müller; M. Brunner
The neurotoxic effects and cerebrospinalfluid (CSF) pharma- cokinetics of bleomycin were evaluated in beagles after chronic intraventricular administration twice a week for 8 consecutive weeks. Bleomycin was reasonably well tolerated at doses of 0.067 to 0.3 mg\\/week. Doses higher than 0.3 mg\\/week produced marked elevation of CSF protein levels and a necrotizing vas- culitis within the central nervous system.
Victor A. Levin; Deborah Byrd; Branimir I. Sikic; B. Bill Etiz; Julia Campbell; Janice K. Bereich; Richard L. Davis
S100B is an important brain specific protein for monitoring damage and activation of astrocytes. Using a straight forward, non-resource demanding in-house ELISA technique we measured S100B in cerebrospinalfluid (CSF) and serum in patients with traumatic brain injury (TBI) (serum), subarachnoid hemorrhage (SAH) (CSF, serum), intracranial hemorrhage (ICH) (CSF, serum), normal controls (NC) (serum) and a reference population (CSF, N=409).
A. Petzold; G. Keir; D. Lim; M. Smith; E. J. Thompson
Poly-ADP-ribosylation (PAR) of proteins by poly(ADP-ribose) polymerases (PARP) occurs after experimental traumatic brain injury (TBI) and modulates neurologic outcome. Several promising pharmacological PARP inhibitors have been developed for use in humans, but there is currently no clinically relevant means of monitoring treatment effects. We therefore used an enzyme-linked immunosorbent assay to measure PAR-modified proteins in cerebrospinalfluid (CSF). Cerebrospinalfluid
Ericka L Fink; Yichen Lai; Xiaopeng Zhang; Keri Janesko-Feldman; P David Adelson; Csaba Szabó; Rachel P Berger; Ajit A Sarnaik; Patrick M Kochanek; Robert S B Clark; RSB Clark
Interactions of radiolabelled circulating neuroactive peptides: enkephalin-leucine (Enk-Leu), delta sleep inducing peptide (DSIP), thyrotropin-releasing hormone (TRH) and vasopressin-arginine (VP-Arg) with the blood-brain and blood-cerebrospinalfluid barriers were studied by mean of: 1. a vascular perfusion technique in the guinea-pig using multiple-time brain uptake analysis, 2. a vascular perfusion technique of the in situ isolated choroid plexus from sheep using single-circulation paired-tracer dilution or steady-state analysis. It has been demonstrated that Enk-Leu, DSIP and VP-Arg were taken up intact at the luminal side of the blood-brain barrier and blood-tissue interface of the blood-cerebrospinalfluid barrier by a saturable mechanism. On the other hand, a non-saturable mechanism as well as possible enzymatic degradation were shown during TRH interactions with either the blood-brain or blood-cerebrospinalfluid barriers. It is concluded that both, facilitated and simple diffusion, govern circulating neuroactive peptide uptake into the central nervous system. PMID:2193795
Zlokovic, B V; Segal, M B; Davson, H; Lipovac, M N; Hyman, S; McComb, J G
\\u000a The dynamics of cerebrospinalfluid flow are directly linked to those of the cardiovascular system. The heart not only drives\\u000a blood flow, but is also at the origin of CSF pulsation through the expansion and contraction of cerebral blood vessels. As\\u000a was detailed in the preceding chapter, CSF dynamics can be altered by diseases and conditions such as hydrocephalus and,
Definite diagnosis of meningeal seeding by systemic cancer relies on the presence of malignant cells in the cerebrospinalfluid (CSF). In the absence of such cells in the CSF, only two other tests strongly suggest the diagnosis - a CT scan and a myelogram. This paper reports a case in which the diagnosis was strongly suggested by an unusual uptake of Tc-99m methylene diphosphonate by the leptomeninges during a skeletal scan and later established by the presence of malignant cells in the CSF. The radionuclide scan may be an additional diagnostic test in some cases with meningeal seeding by systemic cancer.
Neuro-Behçet's disease (NBD) is a serious complication of Behçet's disease. Generally, NBD patients with a chronic course are refractory to immunosuppressive treatment, resulting in the deterioration of personality. In this study, levels of B cell-activating factor belonging to the TNF family (BAFF) were measured in the cerebrospinalfluid (CSF) from 18 patients with NBD, 27 patients with epidemic aseptic meningitis (AM), 24 patients with multiple sclerosis (MS) and 34 healthy controls. BAFF levels in patients with NBD were significantly elevated compared with healthy controls, but showed no statistically significant elevation compared with either of the disease controls. In contrast, CSF IL-6 levels were slightly elevated in patients with NBD and significantly elevated in patients with AM and MS compared with healthy controls. Patients with NBD were subdivided into two groups according to their clinical course (eight patients with a slowly progressive course presenting with psychosis and dementia and 10 patients with an acute course including aseptic meningitis, brainstem involvement and myelopathy). BAFF levels were significantly increased in those with a slowly progressive course compared with those with an acute course. CSF BAFF levels did not correlate with serum BAFF levels, CSF cell counts or CSF IL-6 levels in patients with NBD. These data suggested that BAFF was produced within the central nervous system and may be associated with the development of NBD, particularly with a progressive course. PMID:22340436
Neuro-Behçet's disease (NBD) is a serious complication of Behçet's disease. Generally, NBD patients with a chronic course are refractory to immunosuppressive treatment, resulting in the deterioration of personality. In this study, levels of B cell-activating factor belonging to the TNF family (BAFF) were measured in the cerebrospinalfluid (CSF) from 18 patients with NBD, 27 patients with epidemic aseptic meningitis (AM), 24 patients with multiple sclerosis (MS) and 34 healthy controls. BAFF levels in patients with NBD were significantly elevated compared with healthy controls, but showed no statistically significant elevation compared with either of the disease controls. In contrast, CSF IL-6 levels were slightly elevated in patients with NBD and significantly elevated in patients with AM and MS compared with healthy controls. Patients with NBD were subdivided into two groups according to their clinical course (eight patients with a slowly progressive course presenting with psychosis and dementia and 10 patients with an acute course including aseptic meningitis, brainstem involvement and myelopathy). BAFF levels were significantly increased in those with a slowly progressive course compared with those with an acute course. CSF BAFF levels did not correlate with serum BAFF levels, CSF cell counts or CSF IL-6 levels in patients with NBD. These data suggested that BAFF was produced within the central nervous system and may be associated with the development of NBD, particularly with a progressive course.
A 27-year-old woman suffering from systemic lupus erythematosus was admitted because she had motor and sensory palsy of the lower extremities, neck stiffness, and a fever. Cerebrospinalfluid study indicated meningitis, and magnetic resonance imaging revealed cord swelling and high signals at Th9–Th12 levels. Antibiotics treatment led to resolution of the meningeal signs. Intravenous cyclophosphamide and prednisolone resulted in a
The aim of this study was to validate a diagnosis model that provides pABM, the probability of bacterial versus viral meningitis,\\u000a based on four parameters collected at the time of first lumbar tap: cerebrospinalfluid protein level, cerebrospinalfluid\\u000a polymorphonuclear cell count, blood glucose level, and leucocyte count. The model was evaluated prospectively as an aid to\\u000a therapeutic decision-making in
V. Baty; J.-F. Viel; H. Schuhmacher; F. Jaeger; P. Canton; B. Hoen
Increased concentrations of the excitotoxin quinolinic acid (QUIN) have been implicated in the neurologic deficits and brain atrophy that may accompany infection with the human immunodeficiency virus type-1. Key neuropathologic features of the AIDS encephalitis are replicated in some macaques following infection with the simian immunodeficiency virus (SIV). In the present studies, cerebrospinalfluid (CSF) QUIN concentrations increased within 2 weeks following infection of 11 rhesus macaques (Macaca mulatta) with a neurotropic sooty mangabey isolate of the simian immunodeficiency virus (SIVsm) and were sustained to greater than 2 standard deviations above uninfected control macaques. Highest CSF QUIN concentrations (up to 400-fold above pre-inoculation levels) were observed in 6 SIVsm-infected macaques with motor and behavioral abnormalities during life, brain atrophy on MRI scan and inflammatory lesions within the brain and meninges. Four of the 6 neurologic macaques deteriorated rapidly within 12 weeks after inoculation and had substantially larger increases in CSF QUIN levels than 2 other neurologic macaques and 5 macaques without neurologic signs which survived for longer than 37 weeks. Increases in serum QUIN and CSF kynurenic acid also occurred but generally to a lesser degree than the increases in CSF QUIN. In some animals, increases in serum L-kynurenine concentrations and reductions in CSF and serum L-tryptophan occurred and were consistent with activation of indoleamine-2, 3-dioxygenase, the first enzyme of the kynurenine pathway in extrahepatic tissues. CSF QUIN exceeded serum QUIN in 8.8% of samples from macaques with neurologic signs, supporting increased QUIN synthesis within the central nervous system. Production of [13C6]QUIN was demonstrated in one SIVsm-infected macaque and one uninfected control macaque following an intracisternal injection of [13C6]L-tryptophan and suggests that L-tryptophan is a substrate for QUIN synthesis within the nervous system or meninges, although the cellular localization of QUIN synthesis remain to be determined. We conclude that increases in kynurenine pathway metabolism occur in SIV-infected macaques and are most prominent in macaques with neurologic signs. Macaques infected with SIV offer a model to investigate the relationship between the metabolism of neuroactive kynurenines and neurologic disturbances associated with retroviral infection. PMID:1535532
Heyes, M P; Jordan, E K; Lee, K; Saito, K; Frank, J A; Snoy, P J; Markey, S P; Gravell, M
Cerebrospinalfluid (CSF) flow dynamics, which supposedly have a strong relationship with chronic cerebrospinal venous insufficiency (CCSVI), might be expected to be affected in multiple sclerosis (MS) patients. In this study, CSF flow at the level of the cerebral aqueduct was evaluated quantitatively by phase contrast magnetic resonance imaging (PC-MRI) to determine whether CSF flow dynamics are affected in MS patients. We studied 40 MS patients and 40 healthy controls using PC-MRI. We found significantly higher caudocranial (p=0.010) and craniocaudal CSF flow volumes (p=0.015) and stroke volume (p=0.010) in the MS patients compared with the controls. These findings may support the venous occlusion theory, but may also be explained by atrophy-dependent ventricular dilatation independent of the venous theory in MS patients.
Background Bacterial invasion through the blood-cerebrospinalfluid barrier (BCSFB) during bacterial meningitis causes secretion of proinflammatory cytokines/chemokines followed by the recruitment of leukocytes into the CNS. In this study, we analyzed the cellular and molecular mechanisms of polymorphonuclear neutrophil (PMN) and monocyte transepithelial transmigration (TM) across the BCSFB after bacterial infection. Methods Using an inverted transwell filter system of human choroid plexus papilloma cells (HIBCPP), we studied leukocyte TM rates, the migration route by immunofluorescence, transmission electron microscopy and focused ion beam/scanning electron microscopy, the secretion of cytokines/chemokines by cytokine bead array and posttranslational modification of the signal regulatory protein (SIRP) ? via western blot. Results PMNs showed a significantly increased TM across HIBCPP after infection with wild-type Neisseria meningitidis (MC58). In contrast, a significantly decreased monocyte transmigration rate after bacterial infection of HIBCPP could be observed. Interestingly, in co-culture experiments with PMNs and monocytes, TM of monocytes was significantly enhanced. Analysis of paracellular permeability and transepithelial electrical resistance confirmed an intact barrier function during leukocyte TM. With the help of the different imaging techniques we could provide evidence for para- as well as for transcellular migrating leukocytes. Further analysis of secreted cytokines/chemokines showed a distinct pattern after stimulation and transmigration of PMNs and monocytes. Moreover, the transmembrane glycoprotein SIRP? was deglycosylated in monocytes, but not in PMNs, after bacterial infection. Conclusions Our findings demonstrate that PMNs and monoctyes differentially migrate in a human BCSFB model after bacterial infection. Cytokines and chemokines as well as transmembrane proteins such as SIRP? may be involved in this process.
Detailed outcome data for the management of anterior skull base fractures associated with cerebrospinalfluid (CSF) leakage is lacking. We present detailed follow-up data of a single-center study using a predetermined algorithm for the management of CSF leakage secondary to traumatic fractures. A number of 138 consecutive patients were included in the analysis; all patients underwent high-resolution computed tomography (CT) scanning at time of admission with ?(2)-transferrin testing used to confirm CSF leakage. Patients with acute surgical indications were operated as emergent; leaks were repaired at the time of initial surgery in patients with intracranial pressure?15 cm H(2)O. The remainder of the study population was managed conservatively including use of prophylactic antibiotics; lumbar drainage (LD) catheters were placed in those patients with leakage persisting beyond 48 h. Leaks lasting longer than 5 days underwent microsurgical repair using an intradural bicoronal approach. One-year follow-up assessment included evaluation of neurological status, Glasgow Outcome Scale (GOS), and repeat head CT. Twenty eight patients (26.9%) underwent emergent surgery, 15 of whom had simultaneous CSF leak repair, whereas 76 patients (73.1%) underwent delayed CSF leak repair between days 5 and 14. Postoperative meningitis rate was low (1.9%). Postoperative CSF leak (1.9%) was managed by intradural or transnasal endoscopic operation. Comparable rates of anosmia and frontal lobe hypodensities were seen in the surgical and conservatively managed subgroups. The presented algorithm, utilizing prophylactic antibiotics, trial of LD, acute and/or delayed intradural microsurgery, yields favorable outcomes. Large randomized controlled trials are needed to better define the role of prophylactic antibiotics and to better characterize the optimal timing and approach of surgical repair. PMID:21947554
Sherif, Camillo; Di Ieva, Antonio; Gibson, Daniel; Pakrah-Bodingbauer, Bita; Widhalm, Georg; Krusche-Mandl, Irena; Erdoes, Jozsef; Gilloon, Benjamin; Matula, Christian
Quinolinic acid is an "excitotoxic" metabolite and an agonist of N-methyl-D-aspartate receptors. Of patients infected with human immunodeficiency virus type 1 (HIV-1) who were neurologically normal or exhibited only equivocal and subclinical signs of the acquired immunodeficiency syndrome (AIDS) dementia complex, concentrations of quinolinic acid in cerebrospinalfluid (CSF) were increased twofold in patients in the early stages of disease (Walter Reed stages 1 and 2) and averaged 3.8 times above normal in later-stage patients (Walter Reed stages 4 through 6). However, in patients with either clinically overt AIDS dementia complex, aseptic meningitis, opportunistic infections, or neoplasms, CSF levels were elevated over 20-fold and generally paralleled the severity of cognitive and motor dysfunction. CSF concentrations of quinolinic acid were significantly correlated to the severity of the neuropsychological deficits. After treatment of AIDS dementia complex with zidovudine and treatment of the opportunistic infections with specific antimicrobial therapies, CSF levels of quinolinic acid decreased in parallel with clinical neurological improvement. By analysis of the relationship between levels of quinolinic acid in the CSF and serum and integrity of the blood-brain barrier, as measured by the CSF:serum albumin ratio, it appears that CSF levels of quinolinic acid may be derived predominantly from intracerebral sources and perhaps from the serum. While quinolinic acid may be another "marker" of host- and virus-mediated events in the brain, the established excitotoxic effects of quinolinic acid and the magnitude of the increases in CSF levels of the acid raise the possibility that quinolinic acid plays a direct role in the pathogenesis of brain dysfunction associated with HIV-1 infection. PMID:1826418
Heyes, M P; Brew, B J; Martin, A; Price, R W; Salazar, A M; Sidtis, J J; Yergey, J A; Mouradian, M M; Sadler, A E; Keilp, J
Isoelectric focusing (IEF) coupled with immunodetection (immunofixation or immunoblotting) has become the leading technique for the detection and study of oligoclonal bands (OCBs) in cerebrospinalfluid (CSF) and also is increasingly used in other body fluids such as the tear and serum. Limited commercial availability of precast agarose IEF gels for research and a need for customization prompted reporting a detailed general protocol for the preparation and casting of agarose IEF gel along with sample, control, and isoelectric point marker preparation and carrying out the focusing itself for CSF OCBs. However, the method is readily adaptable to the use of other body fluid specimens and, possibly, research specimens such as culture fluids as well. PMID:22585491
A variety of associated lesions may require the neurosurgeon's assistance in the management of bacterial meningitis. As treatment of this infection of the central nervous system proceeds, the surgeon will have to decide about the concurrent or subsequent operative treatment of congenital dysraphic states, paraneural infections, compound fractures or penetrating wounds of thecranium or spine, or infected bypass shunts for cerebrospinalfluid (CSF). In patients with intractable meningitic infections the surgeon may have to insert a ventricular drainage-irrigation system to permit adequate perfusion of the CSF pathways with antibiotic. Hydrocephalus or subdural effusions complicating meningitis may bring the patient to the surgeon long after the infection has been cured. This paper examines these problems and outlines the current principles of management. Images FIG. 1 FIG. 2
Background Ventriculoperitoneal shunt (VPS) placement is an established procedure for the treatment of hydrocephalus of diverse etiologies in children and adults. Abdominal cerebrospinalfluid pseudocyst, which is potentially life threatening, is a rare complication and usually occurs during childhood. However, with increasing longevity following successful treatment, it can also occur in adults. Case presentation Here we describe a 22-year-old man who was admitted to our hospital because of diffuse abdominal distention. A VPS was placed 21 years earlier to treat hydrocephalus secondary to spina bifida. Abdominal computed tomography (CT) revealed a homogeneous low-density fluid collection adjacent to the VPS catheter tip, causing stomach obstruction. Thus a peritoneal pseudocyst around VPS was suspected and emergency laparotomy was performed. The large mass was localized in the left upper abdomen between the stomach and mesentery of the transverse colon, exactly at the omental bursa. The cystic mass was opened and 1500 ml of clear fluid was drained; the distal end of the VPS was repositioned outside the mass. Thus, an abdominal cerebrospinalfluid pseudocyst as a complication of VPS was diagnosed. Conclusion Gastroenterological surgeons should be aware of this possible complication, and this complication should be considered during differential diagnosis of an acute abdomen complaint.
The best treatment for clival chordoma is obtained with total surgical excision, sometimes combined with adjuvant radiotherapy. A cerebrospinalfluid (CSF) fistula is a fatal complication that may occur following extended transsphenoidal surgery (TSS) and adjuvant radiotherapy. We report a case of fulminant meningitis without a CSF fistula in a 57-year-old woman who underwent TSS and multiple radiotherapies for a clival chordoma. She presented to our emergency room with copious epistaxis and odor inside her nasal cavity and had an unexpected fatal outcome. She was diagnosed with meningitis based on CSF culture and blood culture. While treating clival chordomas with adjuvant radiotherapy, clinicians should be aware of the possibility of fulminant meningitis.
Park, Hyun Wook; Park, Moon Sun; Chung, Seung Young; Park, Ki Seok; Lee, Do Sung; Oh, Jung Tae
Bipolar disorder is a psychiatric disorder characterized by recurrent episodes of mania/hypomania and depression. Progressive cognitive dysfunction such as impairments in executive function and verbal memory is common in euthymic bipolar patients. The cerebrospinalfluid has previously been used to study neurodegenerative processes in Alzheimer's disease, from which changes in three core biomarkers have emerged as indicative of degeneration: amyloid ?, total tau, and hyperphosphorylated tau. Here, neurodegeneration in bipolar disorder was investigated by assessing the association between bipolar disorder and cerebrospinalfluid biomarkers for neurodegenerative processes. Cerebrospinalfluid was obtained from 139 bipolar disorder patients and 71 healthy controls. Concentrations of total and phosphorylated tau, amyloid ?1-42, amyloid ?38/?40/?42, and the soluble forms of amyloid precursor protein were measured in patients vs controls. The concentrations of the soluble forms of amyloid precursor protein were significantly lower in bipolar patients compared with controls. The amyloid ?42/amyloid ?38 and the amyloid ?42/amyloid ?40 ratios were higher in bipolar patients than controls. There were no discernible differences in the concentrations of total/phosphorylated tau, amyloid ?1-42, or amyloid ?38/?40/?42. The concentrations of the biomarkers within the bipolar patient group were further associated with different ongoing medical treatments and diagnostic subgroups. The findings suggest that the amyloid precursor protein metabolism is altered in bipolar disorder. The results may have implications for the understanding of the pathophysiology of bipolar disorder and for the development of treatment strategies. Importantly, there were no signs of an Alzheimer-like neurodegenerative process among bipolar patients.
Jakobsson, Joel; Zetterberg, Henrik; Blennow, Kaj; Johan Ekman, Carl; Johansson, Anette G M; Landen, Mikael
Recent advances in the identification of susceptibility genes and environmental exposures provide strong support that narcolepsy-cataplexy is an immune-mediated disease. Only few serum cytokine studies with controversial results were performed in narcolepsy and none in the cerebrospinalfluid. We measured a panel of 12 cytokines by a proteomic approach in the serum of 35 patients with narcolepsy-cataplexy compared to 156 healthy controls, and in the cerebrospinalfluid of 34 patients with narcolepsy-cataplexy compared to 17 non-narcoleptic patients; and analyzed the effect of age, duration and severity of disease on the cytokine levels. After multiple adjustments we reported lower serum IL-2, IL-8, TNF-?, MCP-1 and EGF levels, and a tendency for higher IL-4 level in narcolepsy compared to controls. Significant differences were only found for IL-4 in cerebrospinalfluid, being higher in narcolepsy. Positive correlations were found in serum between IL-4, daytime sleepiness, and cataplexy frequency. The expression of some pro-inflammatory cytokines (MCP-1, VEGF, EGF, IL2, IL-1?, IFN-?) in either serum or CSF was negatively correlated with disease severity and duration. No correlation was found for any specific cytokine in 18 of the patients with narcolepsy with peripheral and central samples collected the same day. Significant decreased pro/anti-inflammatory cytokine profiles were found at peripheral and central levels in narcolepsy, together with a T helper 2/Th1 serum cytokine secretion imbalance. To conclude, we showed some evidence for alterations in the cytokine profile in patients with narcolepsy-cataplexy compared to controls at peripheral and central levels, with the potential role of IL-4 and significant Th1/2 imbalance in the pathophysiology of narcolepsy. PMID:24394344
In most tissues and organs, the lymphatic circulation is responsible for the removal of interstitial protein and fluid but the parenchyma of the brain and spinal cord is devoid of lymphatic vessels. On the other hand, the literature is filled with qualitative and quantitative evidence supporting a lymphatic function in cerebrospinalfluid (CSF) absorption. The experimental data seems to warrant
Summary \\u000a Objective. To determine whether sFas, caspase-3, proteins which propagate apoptosis, and bcl-2, a protein which inhibits apoptosis, would be increased in cerebrospinalfluid (CSF) in patients with severe traumatic brain\\u000a injury (TBI) and to examine the correlation of sFas, caspase-3, and bcl-2 with each other and with clinical variables.\\u000a \\u000a \\u000a Methods. sFas, caspase-3, and bcl-2 were measured in CSF of
M. Uzan; H. Erman; T. Tanriverdi; G. Z. Sanus; A. Kafadar; H. Uzun
Positive contrast cisternography with digital subtraction of fluoroscopy images before computed tomography (CT) was employed in the investigation of eight patients with cerebrospinalfluid (CSF) rhinorrhoea. Fistulae were visualised by preliminary digital subtraction cisternography (DSC) in six patients and in five patients the sites of leakage were confirmed at surgery. Fluoroscopy facilitated interpretation of CT in all the positive studies and in two patients provided information which could not be deduced from CT cisternography (CTC) alone. The combined technique is recommended for the investigation of patients with recurrent and post operative CSF rhinorrhoea and when CTC alone fails to identify the site of leakage. Images
Byrne, J V; Ingram, C E; MacVicar, D; Sullivan, F M; Uttley, D
Protozoal merozoites were identified in the cerebrospinalfluid of two sheep with neurological disease in the UK. Polymerase chain reaction (PCR) identified the merozoites as Sarcocystis capracanis, a common protozoal pathogen of goats. This is the first report of this species infecting sheep and may represent an aberrant infection with sheep acting as dead end hosts, or alternatively could indicate that sheep are able to act as intermediate hosts for S. capracanis, widening the previously reported host range of this pathogen. It is possible that S. capracanis is a previously unrecognised cause of ovine protozoal meningoencephalitis (OPM) in the UK. PMID:23312871
Formisano, P; Aldridge, B; Alony, Y; Beekhuis, L; Davies, E; Del Pozo, J; Dunn, K; English, K; Morrison, L; Sargison, N; Seguino, A; Summers, B A; Wilson, D; Milne, E; Beard, P M
P300 and cerebrospinalfluid neurotransmitter metabolites and amino acids were examined in 10 patients with Alzheimer's disease, 9 patients with vascular dementia and 10 healthy controls. A negative correlation between P300 amplitude and MHPG concentration, negative correlation between P200 and N200 latencies and norepinephrine concentration, positive correlation between N200 latency and lysine concentration and positive correlation between N100 amplitude and tyrosine concentration were statistically significant. These findings suggest that the noradrenergic system influences P300 amplitude, and that multiple systems may influence P300 components. PMID:9472419
Neurologic symptoms can be the initial manifestation of haemophagocytic lymphohistiocytosis (HLH). In this case study, we present a 3-year old boy with a clinical picture of encephalitis, a cerebrospinalfluid (CSF) protein level up to 1165 mg/dl and diffuse cerebral MRI abnormalities. The diagnosis of HLH was established only 6 weeks after initial presentation. The boy recovered after HLH therapy with persisting mild cognitive defects. Genetic investigation demonstrated X-linked lymphoproliferative disease (XLP) as the underlying cause of HLH. The extremely elevated protein level in CSF in this case has not yet been reported in patients with HLH. PMID:24433830
Introduction An abdominal pseudocyst is a rare complication of a ventriculo-peritoneal shunt. Etiological factors include infection, obstruction and dislodgement. This is the first report of a hepatic cerebrospinalfluid pseudocyst mimicking hydatid liver disease. Case presentation We report the case of an 18-year-old Caucasian male patient who presented with a hepatic pseudocyst secondary to a ventriculo-peritoneal shunt, misdiagnosed as hydatid disease of the liver. Conclusion Hepatic pseudocysts, a rare complication of a ventriculo-peritoneal shunt, have similar clinical and radiological characteristics to those of hydatid liver disease. The formation of a pseudocyst should always be considered in patients with ventriculo-peritoneal shunts in situ.
A 65-year-old man with sudden back pain was transferred to our hospital by ambulance, who also complained of sensory and motor disorder of bilateral legs on arrival. The neurological disorder was gradually aggravated and paraplegia below the level of Th10 was manifested. Computed tomography demonstrated DeBakey IIIb acute aortic dissection; therefore, the paraplegia was thought to be due to spinal cord ischemia caused by the acute aortic dissection. Emergent cerebrospinalfluid drainage was performed, and it was very effective for the relief from paraplegia. The hospital course after the drainage was uneventful and he was discharged on the 39th day after the onset of symptoms.
Clinical (Chvostek symptom and Trousseau-Bonsdorf test) and electromyographical investigations of the neuromuscular excitability were performed in patients with different forms of epilepsy. Ionized Ca, Na, K, Cl, and total Mg were measured in the cerebrospinalfluid (CSF). Seventy-five percent of the patients showed clinical and electromyographic signs of the tetanic syndrome. In patients with general seizures the CSF ionized Ca content was decreased as related to that of normal subjects. Brain and neuromuscular excitability increase was related with the shifts in Ca metabolism. PMID:3188753
Ve?n, A M; Biniaurishvili, R G; Masteropulo, A P; Ba?dauletov, I O; Estrov, V G
We report Campylobacter fetus meningitis associated with endocarditis in a 75-year-old diabetic man after he consumed raw liver. C. fetus was isolated from blood samples and cerebrospinalfluid. Cure was obtained with combined intravenous imipenem-gentamicin for 4 weeks; no relapse occurred after 6 months of follow-up.
Le Du, Damien; Roux, Anne-Laure; Hanachi, Mouna; Dinh, Aurelien; Cremieux, Anne-Claude
The performance of antibody detection, antigen detection, and Aspergillus genus-specific PCR for diagnosing Aspergillus meningitis was investigated with 26 cerebrospinalfluid (CSF) samples obtained from a single patient with proven infection caused by Aspergillus fumigatus. Immunoglobulin G antibodies directed against Aspergillus were not detected by enzyme-linked immunosorbent assay in CSF or serum. The antigen galacto- mannan was detected in the
PAUL E. VERWEIJ; KEES BRINKMAN; HERBERT P. H. KREMER; BART-JAN KULLBERG; JACQUES F. G. M. MEIS
Mumps virus (MuV) was detected in the cerebrospinalfluid (CSF) of 6 of 158 patients with meningitis or encephalitis in absence of clinical mumps in the context of mumps epidemics. Our results suggest the need for the study of MuV RNA in the CSF of neurological patients in this context. PMID:24674094
Bárcena-Panero, Ana; de Ory, Fernando; Castellanos, Ana; Echevarría, Juan E
Multiple myeloma is a hematolymphoid malignancy, and patients with this disorder are frequently complicated by infection. An 80-year-old woman with multiple myeloma was complicated by bacterial meningitis, and was admitted to our hospital in August 2007. She initially received ceftriaxone, but culture of cerebrospinalfluid detected Listeria monocytogenes. Ampicillin was administered, but headache and pyrexia persisted for 2 weeks, and on cerebrospinalfluid examination, the proliferation of polymorphonuclear leukocytes had not resolved. After medication with meropenem was started, the clinical symptoms completely disappeared, and the abnormalities on cerebrospinalfluid examination resolved. The patient ultimately received meropenem for 27 days, resulting in a cure. In conclusion, meropenem is useful to treat bacterial meningitis caused by L. monocytogenes. This agent is indicated when ampicillin shows inadequate effect or if the patient has an allergy to ampicillin. PMID:20112040
Streptococcus pneumoniae (pneumococcus) is a major human pathogen causing pneumonia, sepsis and bacterial meningitis. Using a clinical phenotype based approach with bacterial whole-genome sequencing we identified pneumococcal arginine biosynthesis genes to be associated with outcome in patients with pneumococcal meningitis. Pneumococci harboring these genes show increased growth in human blood and cerebrospinalfluid (CSF). Mouse models of meningitis and pneumonia showed that pneumococcal strains without arginine biosynthesis genes were attenuated in growth or cleared, from lung, blood and CSF. Thus, S. pneumoniae arginine synthesis genes promote growth and virulence in invasive pneumococcal disease. PMID:24338350
Piet, Jurgen R; Geldhoff, Madelijn; van Schaik, Barbera D C; Brouwer, Matthijs C; Valls Seron, Mercedes; Jakobs, Marja E; Schipper, Kim; Pannekoek, Yvonne; Zwinderman, Aeilko H; van der Poll, Tom; van Kampen, Antoine H C; Baas, Frank; van der Ende, Arie; van de Beek, Diederik
An external beam PIXE system was optimized for the determination of the extremely low trace element content of normal cerebrospinalfluid. In order to improve the detection limits of the elements of interest, the ultrafiltrated cerebrospinalfluid samples were deposited onto ultrathin Formvar foils and measured in a helium atmosphere. Since the main emphasis was on copper, the absorber used in the measurements was optimized to give a favourable peak/background ratio for this element. The resulting detection limits for Fe, Cu, Zn and Br were (6.3 ± 2.9), (4.1 ± 1.4), (8.5 ± 2.6) and (18.1 ± 1.1) ppb, respectively. This allowed sufficiently precise determination of the low elemental concentrations in 50 ?l of human cerebrospinalfluid.
Kupila-Rantala, T.; Hyvönen-Dabek, M.; Dabek, J. T.
Nonhuman primates (NHPs) are useful for the study of age-associated changes in the brain as a model that is biologically closely related to humans. For example, with age, all NHPs analyzed to date, develop ?-amyloid (A?) plaques as seen in humans. Nevertheless, it is still unclear if NHPs have human-like age-associated changes in A? and tau protein in cerebrospinalfluid. The present study was an attempt to specifically address these issues. Cerebrospinalfluid levels of A? and phosphorylated tau were measured in 37 and 22 cynomolgus monkeys, respectively, with ages ranging from 4 to 22-year-old. The result from the present study revealed significant age-associated declines in A?42 levels but not in A?40 and phosphorylated tau levels. This finding appears to parallel changes seen with human aging, in which decreased levels of A?42 can be seen in normal older adults, and supporting that cynomolgus monkeys would be a useful model for studying age-related neurologic disorders associated with Alzheimer-like cerebral proteopathy. PMID:24581480
A fully mechanized, computer-controlled, multicommutated flow analysis (MCFA) system dedicated for total protein determination in cerebrospinalfluid samples has been developed. For the protein determination the Exton method has been applied. Dedicated turbidimetric and nephelometric flow-through detectors operating according to paired-emitter detector diode principle have been fabricated by integration of two or three respective light emitting diodes. The developed MCFA system is characterized by robust, compact design and low consumption of the sample (72?L). The limits of detection for turbidimetric and nephelometric detection mode are 65mgL(-1) and 9mgL(-1), respectively. For turbidimetric measurements the range of linear response offered by the MCFA system is 72-900mgL(-1), whereas in the case of nephelometric detection 18-500mgL(-1) linear range is obtained. The throughput of the MCFA system is over 30 injection per hour. The analytical system was optimized with bovine serum albumin standards and successfully validated with real samples of human cerebrospinalfluid. PMID:25059127
Strzelak, Kamil; Wi?niewska, Agnieszka; Bobilewicz, Dagna; Koncki, Robert
Because normal cerebrospinalfluid (CSF) has almost no natural Doppler scatterers, patency testing of ventriculoperitoneal cerebrospinalfluid shunts (small silastic tubing with lumen diameter of approximately 1 mm draining excessive CSF from the brain) cannot be performed by Doppler ultrasound. We have developed a low-frequency bubble excitation system that generates microbubble scatterers in both distilled water and CSF. Doppler ultrasound can then be used for flow measurement in a ventriculoperitoneal shunt. By using low duty-cycle (approximately 10%), low-frequency (approximately 30 kHz), and low-amplitude (approximately 30 kPa) ultrasound, a population of microbubbles can be maintained for sufficiently long times (>10 min) for Doppler ultrasound measurement, although bubble initiation is inconsistent. The minimum pressure needed for bubble maintenance was found to decrease with increasing burst length and duty cycle. It has been possible to detect the presence of CSF shunt flow down to a mean flow rate of 3 mL/h (mean velocity approximately 0.6 mm/s). The bubble maintenance scheme developed satisfies the safety parameters specified by the American Institute of Ultrasound in Medicine (AIUM) and the US Food and Drug Administration (FDA). Results from both in vitro and in vivo (externalized shunts) experiments indicate the feasibility of this scheme for determining realistic CSF shunt flows, though some practical problems remain before the technique will be ready for clinical use. PMID:10374981
Cerebrospinalfluid (CSF) samples from 33 patients with Alzheimer dementia (AD), 21 patients with mild cognitive impairment who converted to AD during followup (MCI-AD), 25 patients with stable mild cognitive impairment (MCI-stable), and 16 nondemented subjects (ND) were analyzed with a chemiluminescence immunoassay to assess the levels of the mitogen-activated protein kinase ERK1/2 (extracellular signal-regulated kinase 1/2). The results were evaluated in relation to total Tau (tTau), phosphorylated Tau (pTau), and beta-amyloid 42 peptide (A?42). CSF-ERK1/2 was significantly increased in the AD group as compared to stable MCI patients and the ND group. Western blot analysis of a pooled cerebrospinalfluid sample revealed that both isoforms, ERK1 and ERK2, and low amounts of doubly phosphorylated ERK2 were detectable. As a predictive diagnostic AD biomarker, CSF-ERK1/2 was inferior to tTau, pTau, and A?42.
Background The mechanism(s) of nociceptive dysfunction and potential roles of opioid neurotransmitters are unresolved in the chronic pain syndromes of fibromyalgia and chronic low back pain. Methods History and physical examinations, tender point examinations, and questionnaires were used to identify 14 fibromyalgia, 10 chronic low back pain and 6 normal control subjects. Lumbar punctures were performed. Met-enkephalin-Arg6-Phe7 (MEAP) and nociceptin immunoreactive materials were measured in the cerebrospinalfluid by radioimmunoassays. Results Fibromyalgia (117.6 pg/ml; 85.9 to 149.4; mean, 95% C.I.; p = 0.009) and low back pain (92.3 pg/ml; 56.9 to 127.7; p = 0.049) groups had significantly higher MEAP than the normal control group (35.7 pg/ml; 15.0 to 56.5). MEAP was inversely correlated to systemic pain thresholds. Nociceptin was not different between groups. Systemic Complaints questionnaire responses were significantly ranked as fibromyalgia > back pain > normal. SF-36 domains demonstrated severe disability for the low back pain group, intermediate results in fibromyalgia, and high function in the normal group. Conclusions Fibromyalgia was distinguished by higher cerebrospinalfluid MEAP, systemic complaints, and manual tender points; intermediate SF-36 scores; and lower pain thresholds compared to the low back pain and normal groups. MEAP and systemic pain thresholds were inversely correlated in low back pain subjects. Central nervous system opioid dysfunction may contribute to pain in fibromyalgia.
Baraniuk, James N; Whalen, Gail; Cunningham, Jill; Clauw, Daniel J
Despite many successful applications of Chinese herbal medicine (CHM) in the treatment and prevention of neurological diseases (ND), the fully scientific understanding of CHM's action mechanisms had been hampered for lack of appropriate methods to explore the combinatorial rules, the synergistic mechanisms, and the molecular basis of CHM. As an improved pharmacology approach, cerebrospinalfluid pharmacology (CSFP), based on the fact that cerebrospinalfluid plays an important role in the health maintenance of specific survival environment for neurons and glial cells, has been constructed and applied to CHM research for treating ND. In the present review, the concept and advantages of CSFP are briefly introduced. The approaches and key technologies of CSFP in CHM research are also collated and analyzed. Furthermore, the developing tendency of CSFP is summarized, and its framework in CHM research is also proposed. In summary, CSFP provides a new strategy not only to eliminate some barriers of CHM research for treating ND, but also to broaden the pharmacology research for bridging the gap between CHM and modern medicine. Moreover, the advancements in CSFP will bring about a conceptual move in active ingredients discovery of CHM and make a significant contribution to CHM modernization and globalization.
Chromatography under acid dissociating conditions in conjunction with radioimmunoassay has been employed to investigate the nature of peptides related to opiocortin in human cerebrospinalfluid. Samples of cerebrospinalfluid (CSF) were collected for chromatography from 15 patients prior to air encephalography. 2 patients had pituitary dependent Cushing's disease, 3 non-endocrine neurological disease and 10 non-ACTH related pituitary disease. The column fractions were assayed for N- and C-terminal beta-lipotropin, N-terminal ACTH and gamma-MSH immunoreactivity. Elution profiles obtained from chromatography on Sephadex G-50 demonstrated peaks of immunoreactivity corresponding to the elution positions of synthetic human beta-endorphin, highly purified beta-lipotropin and highly purified gamma-lipotropin in all CSF samples. A peak of a large molecular weight material with N and C terminal beta-lipotropin immunoreactivity was also detected. Chromatography of CSF on Sephadex G-75 showed this large molecular weight peak to be comprised of peptides eluting in the positions of a 31K molecular weight marker with beta-lipotropin and ACTH immunoreactivity and a 16K molecular weight marker with gamma-MSH immunoreactivity. This suggests the presence of the common precursor to ACTH and LPH in the CSF. PMID:7219672
McLoughlin, L; Lowry, P J; Ratter, S J; Hope, J; Besser, G M; Rees, L H
Recent studies indicate that small amyloid-? peptide (A?) oligomers are the major toxic species responsible for development and progression of Alzheimer's disease (AD). Therefore, we suggest that the number of A? oligomers in body fluids is the most direct and relevant biomarker for AD. Determination of the A? oligomer content of cerebrospinalfluid (CSF) samples from 14 AD patients and 12 age-matched controls revealed a clear distinction between both groups. All samples of the control group showed homogenously low numbers of A? oligomers, while the samples of the AD group exhibited significantly higher levels of A? oligomers. The A? oligomer numbers correlated with the patients' Mini-Mental State Examination scores. This indicates that the quantity of A? oligomers in CSF reflects the severity of the disease and that A? oligomers play a crucial role in AD pathology and in turn can be used as a diagnostic biomarker. PMID:23313925
ABSTRACT Epilepsy is a common neurological disorder with seizures, but diagnostic approaches in veterinary clinics remain limited. Cerebrospinalfluid (CSF) is a body fluid used for diagnosis in veterinary medicine. In this study, we explored canine epilepsy diagnostic biomarkers using gas chromatography-mass spectrometry (GC-MS)-based metabolic profiling of CSF and multivariate data analysis. Profiles for subjects with idiopathic epilepsy differed significantly from those of healthy controls and subjects with symptomatic epilepsy. Among 60 identified metabolites, the levels of 20 differed significantly among the three groups. Glutamic acid was significantly increased in idiopathic epilepsy, and some metabolites including ascorbic acid were changed in both forms of epilepsy. These findings show that metabolic profiles of CSF differ between idiopathic and symptomatic epilepsy and that metabolites including glutamic acid and ascorbic acid in CSF may be useful for diagnosis of canine epilepsy.
Hemophagocytic Lymphohistiocytosis (HLH) implies a benign generalized histiocytic proliferate with erythrophagocytosis and it includes familial hemophagocytic lymphohistiocytosis and secondary hemophgocytosis. Spinal fluid changes like mild to moderate pleocytosis (most of the cells are lymphocytes and macrophages) and sometimes hemophagocytosis are seen in primary HLH but are not reported in secondary HLH. Here we report a case of a previously healthy 10 months old male infant who was diagnosed as familial HLH with evidence of CSF hemophagocytosis. He was started on the HLH 2004 treatment protocol with no improvement. A second bone marrow aspiration revealed leshmania donovani antibodies and he was started on anti-leishmania treatment with dramatic response.To the best of our knowledge, this is the first case of secondary HLH with evidence of hemophagocytosis in cerebrospinalfluid. PMID:21748112
Hemophagocytic Lymphohistiocytosis (HLH) implies a benign generalized histiocytic proliferate with erythrophagocytosis and it includes familial hemophagocytic lymphohistiocytosis and secondary hemophgocytosis. Spinal fluid changes like mild to moderate pleocytosis (most of the cells are lymphocytes and macrophages) and sometimes hemophagocytosis are seen in primary HLH but are not reported in secondary HLH. Here we report a case of a previously healthy 10 months old male infant who was diagnosed as familial HLH with evidence of CSF hemophagocytosis. He was started on the HLH 2004 treatment protocol with no improvement. A second bone marrow aspiration revealed leshmania donovani antibodies and he was started on anti-leishmania treatment with dramatic response.To the best of our knowledge, this is the first case of secondary HLH with evidence of hemophagocytosis in cerebrospinalfluid.
The traditional model of cerebrospinalfluid (CSF) hydrodynamics is being increasingly challenged in view of recent scientific evidences. The established model presumes that CSF is primarily produced in the choroid plexuses (CP), then flows from the ventricles to the subarachnoid spaces, and is mainly reabsorbed into arachnoid villi (AV). This model is seemingly based on faulty research and misinterpretations. This literature review presents numerous evidence for a new hypothesis of CSF physiology, namely, CSF is produced and reabsorbed throughout the entire CSF-Interstitial fluid (IF) functional unit. IF and CSF are mainly formed and reabsorbed across the walls of CNS blood capillaries. CP, AV and lymphatics become minor sites for CSF hydrodynamics. The lymphatics may play a more significant role in CSF absorption when CSF-IF pressure increases. The consequences of this complete reformulation of CSF hydrodynamics may influence applications in research, publications, including osteopathic manual treatments. PMID:23768280
Epilepsy is a common neurological disorder with seizures, but diagnostic approaches in veterinary clinics remain limited. Cerebrospinalfluid (CSF) is a body fluid used for diagnosis in veterinary medicine. In this study, we explored canine epilepsy diagnostic biomarkers using gas chromatography-mass spectrometry (GC-MS)-based metabolic profiling of CSF and multivariate data analysis. Profiles for subjects with idiopathic epilepsy differed significantly from those of healthy controls and subjects with symptomatic epilepsy. Among 60 identified metabolites, the levels of 20 differed significantly among the three groups. Glutamic acid was significantly increased in idiopathic epilepsy, and some metabolites including ascorbic acid were changed in both forms of epilepsy. These findings show that metabolic profiles of CSF differ between idiopathic and symptomatic epilepsy and that metabolites including glutamic acid and ascorbic acid in CSF may be useful for diagnosis of canine epilepsy. PMID:24334864
Glaucoma is one of the most common causes of blindness in the world. Well-known risk factors include age, race, a positive family history and elevated intraocular pressures. A newly proposed risk factor is decreased cerebrospinalfluid pressure (CSFP). This concept is based on the notion that a pressure differential exists across the lamina cribrosa, which separates the intraocular space from the subarachnoid fluid space. In this construct, an increased translaminar pressure difference will occur with a relative increase in elevated intraocular pressure or a reduction in CSFP. This net change in pressure is proposed to act on the tissues within the optic nerve head, potentially contributing to glaucomatous optic neuropathy. Similarly, patients with ocular hypertension who have elevated CSFPs, would enjoy a relatively protective effect from glaucomatous damage. This review will focus on the current literature pertaining to the role of CSFP in glaucoma. Additionally, the authors examine the relationship between glaucoma and other known CSFP-related ophthalmic disorders.
A semi-quantitative ELISA, using variable surface glycoprotein of T.b. gambiense as antigen, was developed for the detection of antibodies of different immunoglobulin isotypes in serum and cerebrospinalfluid of sleeping sickness patients. Using the assay, the antibody profiles of paired serum and cerebrospinalfluid samples of 28 patients have been studied. Total concentrations of various Ig isotypes were determined as
V Lejon; P Büscher; E Magnus; A Moons; I Wouters; N Van Meirvenne
We previously identified CCL20 as an early chemokine in the cerebrospinalfluid (CSF) of patients with pneumococcal meningitis but its functional relevance was unknown. Here we studied the role of CCL20 and its receptor CCR6 in pneumococcal meningitis. In a prospective nationwide study, CCL20 levels were significantly elevated in the CSF of patients with pneumococcal meningitis and correlated with CSF leukocyte counts. CCR6-deficient mice with pneumococcal meningitis and WT mice with pneumococcal meningitis treated with anti-CCL20 antibodies both had reduced CSF white blood cell counts. The reduction in CSF pleocytosis was also accompanied by an increase in brain bacterial titers. Additional in vitro experiments showed direct chemoattractant activity of CCL20 for granulocytes. In summary, our results identify the CCL20-CCR6 axis as an essential component of the innate immune defense against pneumococcal meningitis, controlling granulocyte recruitment.
It is unknown which factors determine the changes in cerebrospinalfluid (CSF) pressure inside the craniospinal system during the changes of the body position. To test this, we have developed a new model of the CSF system, which by its biophysical characteristics and dimensions imitates the CSF system in cats. The results obtained on a model were compared to those in animals observed during changes of body position. A new model was constructed from two parts with different physical characteristics. The "cranial" part is developed from a plastic tube with unchangeable volume, while the "spinal" part is made of a rubber baloon, with modulus of elasticity similar to that of animal spinal dura. In upright position, in the "cranial" part of the model the negative pressure appears without any measurable changes in the fluid volume, while in "spinal" part the fluid pressure is positive. All of the observed changes are in accordance to the law of the fluid mechanics. Alterations of the CSF pressure in cats during the changes of the body position are not significantly different compared to those observed on our new model. This suggests that the CSF pressure changes are related to the fluid mechanics, and do not depend on CSF secretion and circulation. It seems that in all body positions the cranial volume of blood and CSF remains constant, which enables a good blood brain perfusion. PMID:21648311
MicroRNAs (miRNAs) constitute a potent layer of gene regulation by guiding RISC to target sites located on mRNAs and, consequently, by modulating their translational repression. Changes in miRNA expression have been shown to be involved in the development of all major complex diseases. Furthermore, recent findings showed that miRNAs can be secreted to the extracellular environment and enter the bloodstream and other body fluids where they can circulate with high stability. The function of such circulating miRNAs remains largely elusive, but systematic high throughput approaches, such as miRNA profiling arrays, have lead to the identification of miRNA signatures in several pathological conditions, including neurodegenerative disorders and several types of cancers. In this context, the identification of miRNA expression profile in the cerebrospinalfluid, as reported in our recent study, makes miRNAs attractive candidates for biomarker analysis. There are several tools available for profiling microRNAs, such as microarrays, quantitative real-time PCR (qPCR), and deep sequencing. Here, we describe a sensitive method to profile microRNAs in cerebrospinalfluids by quantitative real-time PCR. We used the Exiqon microRNA ready-to-use PCR human panels I and II V2.R, which allows detection of 742 unique human microRNAs. We performed the arrays in triplicate runs and we processed and analyzed data using the GenEx Professional 5 software. Using this protocol, we have successfully profiled microRNAs in various types of cell lines and primary cells, CSF, plasma, and formalin-fixed paraffin-embedded tissues. PMID:24514260
Blood-cerebrospinal barrier (BCB) dysfunction has previously been shown in subjects with schizophrenia and depressed patients with attempted suicide. Bipolar disorder (BPD) shares clinical features with both these disorders, but it is unknown if the integrity of the BCB is altered also in BPD. To assess if BCB function in BPD we surveyed 134 mood-stabilized BPD patients and 86 healthy controls. Serum and cerebrospinalfluid (CSF) samples were collected and analyzed for albumin concentration by immunonephelometry. CSF/serum albumin ratio, an established measure of BCB function, was significantly elevated in BPD patients as compared to controls. After stratifying patients according to diagnostic subtype, BPD I patients had the highest CSF/serum albumin ratios. Moreover, BPD patients on antipsychotic treatment had higher CSF/serum albumin ratio than BPD patients on other treatments. When excluding BPD patients on antipsychotic treatment the difference in CSF/serum albumin ratio between the BPD and control groups disappeared. In conclusion, antipsychotic treatment in BPD is associated with elevated CSF/serum albumin ratio, tentatively as a sign of impaired BCB function. Whether this elevation is caused by antipsychotic treatment or is associated with a certain subtype of BPD, requiring antipsychotic treatment, remains to be determined. PMID:24745469
In light of encephalopathy presenting as autistic regression (autistic encephalopathy, AE) closely following measles-mumps- rubella (MMR) vaccination, three children underwent cerebrospinalfluid (CSF) assessments including studies for measles virus (MV). All three children had concomitant onset of gastrointestinal (GI) symptoms and had already had MV genomic RNA detected in biopsies of ileal lymphoid nodular hyperplasia (LNH). Presence of MV Fusion
J. J. Bradstreet; J. El Dahr; A. Anthony; J. J. Kartzinel; A. J. Wakefield
Cytokines are involved in nerve regeneration by modulating the synthesis of neurotrophic factors. The role played by interleukin-6 (IL-6) in promoting nerve growth factor (NGF) after brain injury was investigated by monitoring the release of IL-6 and NGF in ventricular cerebrospinalfluid (CSF) of 22 patients with severe traumatic brain injuries. IL-6 was found in the CSF of all individuals
Thomas Kossmann; Volkmar Hans; Hans-Georg Imhof; Otmar Trentz; Maria Cristina Morganti-Kossmann
Background: The cerebrospinalfluid (CSF) proteins ?-amyloid 42 (A?42) and Tau are believed to indirectly reflect some core pathological features of Alzheimer’s disease (AD). Their topographic origin and their association with synaptic dysfunction are still not well understood. Aim: The present study aimed to explore possible associations between cerebral glucose metabolism and CSF A?42 as well as Tau protein levels
Ruth Vukovich; Robert Perneczky; Alexander Drzezga; Hans Förstl; Alexander Kurz; Matthias Riemenschneider
Caffeine, the most widely consumed psychoactive drug and a weak adenosine receptor antagonist, can be neuroprotective or neurotoxic depending on the experimental model or neurologic disorder. However, its contribution to pathophysiology and outcome in traumatic brain injury (TBI) in humans is undefined. We assessed serial cerebrospinalfluid (CSF) concentrations of caffeine and its metabolites (theobromine, paraxanthine, and theophylline) by high-pressure
Kathleen T Sachse; Edwin K Jackson; Stephen R Wisniewski; Delbert G Gillespie; Ava M Puccio; Robert S B Clark; C Edward Dixon; Patrick M Kochanek
Background: Cysteine proteases are involved in the extension of cancer into the subarachnoid space. The presence of cathepsins B and H along with their potent inhibitor cystatin C in the cerebrospinalfluid (CSF) was investigated in patients with leptomeningeal metastasis of cancer (LM). Materials and methods: CSF samples were obtained in 16 cases of LM (10 solid tumors and 6
Background: Fluorescence activated cell scanning (FACS) is a useful tool for identifying malignant cell clones of lymphoma cells in cerebrospinalfluid (CSF) by immunological phenotype. Methods: We used FACS analysis for demonstrating it to be a quick and reliable technology that is available in most hematological laboratories. In this study, we demonstrate the clinical application of FACS analysis within a
Sabine Urbanits; Andrea Griesmacher; Georg Hopfinger; Günther Stockhammer; Alireza Karimi; Mathias M. Müller; Elisabeth Pittermann; Wolfgang Grisold
A simple micellar electrokinetic chromatography (MEKC) method with UV detection at 200nm for analysis of piracetam in plasma and in cerebrospinalfluid (CSF) by direct injection without any sample pretreatment is described. The separation of piracetam from biological matrix was performed at 25°C using a background electrolyte consisting of Tris buffer with sodium dodecyl sulfate (SDS) as the electrolyte solution.
BACKGROUND: The parenchyma of the brain does not contain lymphatics. Consequently, it has been assumed that arachnoid projections into the cranial venous system are responsible for cerebrospinalfluid (CSF) absorption. However, recent quantitative and qualitative evidence in sheep suggest that nasal lymphatics have the major role in CSF transport. Nonetheless, the applicability of this concept to other species, especially to
Miles Johnston; Andrei Zakharov; Christina Papaiconomou; Giselle Salmasi; Dianna Armstrong
The FilmArray blood culture identification (BCID) panel is a rapid molecular diagnostic test approved for use with positive blood culture material. We describe a fatal case of meningococcemia with central nervous system (CNS) involvement detected using the BCID test with culture-negative blood and cerebrospinalfluid. PMID:24740076
Pardo, Joe; Klinker, Kenneth P; Borgert, Samuel J; Butler, Brittany M; Rand, Kenneth H; Iovine, Nicole M
The Guillain-Barré syndrome is often preceded by a herpes virus infection. Herpes simplex virus, however, has rarely been observed as the causative agent. A patient is described with a herpes simplex virus infection followed by a Guillain-Barré syndrome. Immunoblotting was used to detect herpes simplex virus-specific antibodies in serum and cerebrospinalfluid. Images
Bernsen, H J; Van Loon, A M; Poels, R F; Verhagen, W I; Frenken, C W
Summary Immunostimulation in the central nervous system (CNS) measured as abnormal intrathecal immunoglobulin production or activated lymphocytes in the cerebrospinalfluid (CSF), was found in 22 of 25 HIV seropositive patients. All of 11 patients with symptomatic HIV infection and nine of 14 asymptomatic patients had an increased IgG index or a Tourtellotte's production number indicating CNS infection. The amount
L. Hagberg; G. Norkrans; A. Forsman; E. Rybo; L. Svennerholm
Light subunit neurofilament (NFL) and glial fibrillary acidic protein (GFAP) concentrations were de- termined in cerebrospinalfluid (CSF) of 34 patients with human African trypanosomiasis (HAT), five serologically positive but parasitologically unconfirmed individuals, and four healthy controls without evidence of HAT. In patients with second stage HAT (n 5 30), NFL levels were abnormally elevated in 10 cases and GFAP
V. LEJON; L. E. ROSENGREN; P. BUSCHER; J.-E. KARLSSON; H. N. SEMA
Diagnosis of central nervous system (CNS) involvement in sleeping sickness is crucial in order to give an appropriate treatment regimen. Neurological symptoms occur late, therefore field diagnosis is based on white blood cell count, total protein concentration and presence of trypanosomes in cerebrospinalfluid (CSF). More sensitive and specific parameters are now available. Blood–CSF barrier (B-CSFB) dysfunction, intrathecal total and
P. M Preux; A Stanghellini; M. O Jauberteau; P Büscher; M Dumas
We investigated the levels of amyloid precursor protein (APP) and ?-amyloid peptide (A?) in the cerebrospinalfluid (CSF) from 110 individuals ranging in age from newborn to 82-years old to analyze their regulation with age. These samples were segregated into two groups; one group contained CSF samples from patients with diagnosed CNS abnormalities and the second group contained CSF samples
R. T. Carroll; M. R. Lust; K. S. Kim; P. D. Doyle; M. R. Emmerling
Background: If cerebrospinalfluid (CSF) human im- munodeficiency virus (HIV) RNA levels are elevated be- fore the development of neuropsychological (NP) im- pairment, such an observation would support prospective monitoring of CSF HIV RNA levels as well as therapeu- tic interventions designed to lower CSF HIV levels. Objective: To determine whether increased CSF HIV RNA levels at an earlier time
Ronald J. Ellis; David J. Moore; Meredith E. Childers; Scott Letendre; J. Allen McCutchan; Tanya Wolfson; Stephen A. Spector; Karen Hsia; Robert K. Heaton; Igor Grant
Presence of bone marrow elements in cerebrospinalfluid is rare. Journal publications on this topic are few and majority of them were written over a decade ago mostly as case reports in young children or the elderly. The increased cellularity and presence of myeloid precursors can be a pitfall and may be misdiagnosed as leukemia or lymphoma or central nervous system infection, when the specimen is actually not representative. With the intention to create awareness of potential pitfalls and avoid erroneous diagnoses, as well as adding on to the current photo archive of bone marrow elements in CSF, we present a recent case of bone marrow contaminants in the CSF of a 16-year-old girl.
Cerebrospinalfluid (CSF) amino acid neurotransmitters, related compounds, and their precursors, choline levels, and acetylcholinesterase activity were measured in the CSF of patients with cerebellar ataxia during a randomized, double-blind, crossover, placebo-controlled clinical trial of physostigmine salicylate. The CSF gamma-aminobutyric acid, methionine, and choline levels, adjusted for age, were significantly lower in patients with cerebellar ataxia compared with controls. Physostigmine selectively reduced the level of CSF isoleucine and elevated the levels of phosphoethanolamine. No change occurred in CSF acetylcholinesterase activity and in the levels of plasma amino compounds in patients with cerebellar ataxia when compared with controls. Median ataxia scores did not statistically differ between placebo and physostigmine nor did functional improvement occur in any of the patients. PMID:1978660
Manyam, B V; Giacobini, E; Ferraro, T N; Hare, T A
External beam PIXE analysis with a 2.4 MeV proton beam was used to determine the concentrations of K, Ca, Fe, Cu, Zn and Br in cerebrospinalfluid from patients having various disorders. The obtained total concentration ranges K 34,000-1,079,000, Ca 5300-81,300, Fe 40-1030, Cu 20-1650, Zn 15-1250 and Br 400-43,000 micrograms/kg are compared with the values given in the literature. In certain patients there were very high CSF bromine levels, but this was shown to be the result of taking medications presented as bromide salts. The possibility of using the method in clinical practice for CSF analysis is considered. The new method of preparing self-supporting films of the samples was used. This method was further optimized by investigating in detail the use of EDTA as a homogenizer. PMID:2980812
Lapatto, R; Hyvönen-Dabek, M; Dabek, J T; Räisänen, J
Proteomic analysis of cerebrospinalfluid (CSF) from patients with temporal lobe epilepsy (TLE) and controls was carried out using two-dimensional gel electrophoresis followed by liquid chromatography electrospray ionization tandem mass spectrometry. Five protein spots showed significant differential expression (p<0.05): vitamin D-binding protein (DBP) was elevated in the CSF of TLE patients whereas cathepsin D, apolipoprotein J, Fam3c, and superoxide dismutase 1 (SOD1) were decreased in the CSF of TLE patients. Additional six protein spots presented only in the CSF of epilepsy patients were identified as tetranectin (TN), talin-2, apolipoprotein E, immunoglobulin lambda light chain (IGL@), immunoglobulin kappa variable light chain 1-5 (IGKV1-5), and procollagen C-endopeptidase enhancer 1 (PCOLCE). Expression of DBP, SOD1 and talin-2 was validated by western blot. Our results may provide better understanding of the pathophysiologic mechanisms underlying epileptogenesis and possible epilepsy biomarkers. PMID:19109932
Schizophrenia is a neurodevelopment disorder in which the interplay of genes and environment contributes to disease onset and establishment. The most consistent pathological feature in schizophrenic patients is an enlargement of the brain ventricles. Yet, so far, no study has related this finding with dysfunction of the choroid plexus (CP), the epithelial cell monolayer located within the brain ventricles that is responsible for the production of most of the cerebrospinalfluid (CSF). Enlarged brain ventricles are already present at the time of disease onset (young adulthood) and, of notice, isolated mild ventriculomegaly detected in utero is associated with subsequent mild neurodevelopmental abnormalities similar to those observed in children at high risk of developing schizophrenia. Here we propose that altered CP/CSF dynamics during neurodevelopment may be considered a risk, causative and/or participating factor for development of schizophrenia.
Pharmacia's "PhastSystem" for semi-automated isoelectric focusing (IEF) in thin precast polyacrylamide gels (PAGE) was found to be as sensitive as high-resolution protein electrophoresis (HRPE) in agarose gels and conventional PAGE-IEF for detection of oligoclonal banding (OB) in concentrated cerebrospinalfluid (CSF) samples. Both PhastSystem IEF and HRPE revealed OB in CSF from eight of nine multiple sclerosis patients and four of 10 patients with various types of infection of the central nervous system as opposed to only two of 70 patients with miscellaneous neuropsychiatric disorders. The PhastSystem also frequently detected OB in silver-stained, unconcentrated CSF from patients with multiple sclerosis. PMID:1688744
Wybo, I; Van Blerk, M; Malfait, R; Goubert, P; Gorus, F
Major depression and posttraumatic stress disorder (PTSD) are often comorbid, resulting in more impairment compared than with either diagnosis alone. Both major depression and PTSD are thought to be associated with monoamine transmitter abnormalities. This study compared clinical features and cerebrospinalfluid (CSF) monoamine metabolites in drug-free depressed subjects with a current major depressive episode (MDE) without comorbid PTSD, subjects with a current MDE and comorbid PTSD, and healthy volunteers. Depressed subjects with comorbid PTSD had higher CSF homovanillic acid (HVA) levels compared with depressed subjects without comorbid PTSD or healthy volunteers. Higher HVA was present after adjustment for sex, lifetime aggression severity and depression scores, alcoholism, tobacco smoking, comorbid cluster B personality disorder, reported childhood abuse, and psychosis. We found no group difference in CSF 5-hydroxyindolacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) levels. Higher dopaminergic activity may contribute to alterations in memory and other cognitive functions, anhedonia, and hypervigilance observed in PTSD. PMID:15695066
Sher, Leo; Oquendo, Maria A; Li, Shuhua; Burke, Ainsley K; Grunebaum, Michael F; Zalsman, Gil; Huang, Yung-yu; Mann, J John
Biotyping, slime production, antibiograms, extrachromosomal DNA banding and total DNA restriction analysis were used to characterize Staphylococcus epidermidis strains causing cerebrospinalfluid shunt infections in 11 patients. Infections considered to be community acquired and those acquired in the first 2 weeks of hospital admission were due to oxacillin-susceptible isolates. Multiply resistant strains were isolated from patients who were in hospital for more than 1 month before tube implantation. Slime was detected in staphylococci for 54% of cases, but its expression varied. Strains from different patients could be differentiated from one another by the extrachromosomal DNA bandings and total DNA restriction patterns, but isolates from the same patient were usually similar. During the period of external drainage, epidemiological markers were useful in differentiating persistence of infection from contamination or re-infection by a new strain. Images Fig. 1
Etienne, J.; Charpin, B.; Grando, J.; Brun, Y.; Bes, M.; Fleurette, J.
Children and adolescents with maltreatment-related posttraumatic stress disorder (PTSD) exhibit smaller intracranial tissue volume than controls. Linear relationships have also been observed between intracranial tissue volume and the age of maltreatment onset. The authors explored associations among adult PTSD, early trauma, and cerebral volumes in 99 combat veterans. A bone-based estimate of cranial volume was developed to adjust for variation in body size. Posttraumatic stress disorder was not associated with smaller cerebral tissue volume, but rather with smaller cerebrospinalfluid (CSF) and cranial volumes. These findings co-occurred with expected effects of alcoholism and aging on cerebral tissue and CSF volumes. The results point to early developmental divergences between groups with and without PTSD following adult trauma. PMID:17955544
Woodward, Steven H; Kaloupek, Danny G; Streeter, Chris C; Kimble, Matthew O; Reiss, Allan L; Eliez, Stephan; Wald, Lawrence L; Renshaw, Perry F; Frederick, Blaise B; Lane, Barton; Sheikh, Javaid I; Stegman, Wendy K; Kutter, Catherine J; Stewart, Lorraine P; Prestel, Rebecca S; Arsenault, Ned J
: Adenosine triphosphate-binding cassette transporter G2 (ABCG2) is expressed on the cerebrospinalfluid (CSF) side of choroid plexus epithelial cells, which form the blood-CSF barrier. Raltegravir was recently identified as a substrate of ABCG2. In the present study, we analyzed the relationship between single-nucleotide polymorphisms of ABCB1 and ABCG2 genes and raltegravir concentrations in 31 plasma and 14 CSF samples of HIV-infected patients treated with raltegravir-containing regimens. The mean CSF raltegravir concentration was significantly lower in CA (25.5 ng/mL) and AA (<10 ng/mL) genotypes at position 421 in ABCG2 gene compared with CC (103.6 ng/mL) genotype holders (P = 0.016). PMID:24872134
Glial fibrillary acidic protein (GFAP) is an established indicator of astrogliosis. Therefore, variable cerebrospinalfluid (CSF) concentrations of this protein might reflect disease-specific pathologic profiles. In patients with narcolepsy, a loss of hypocretin-1 (hcrt-1) neurons in the brain and low concentrations of hcrt-1 in CSF have been reported. We performed a commercially available enzyme-linked immunosorbent assay to investigate if GFAP also is altered in the CSF of these patients. Here we detected significantly higher CSF levels of GFAP in patients with low hcrt-1 levels, of which the majority had a diagnosis of narcolepsy and cataplexy (NC); however, this finding was not observed in patients with hcrt-1 levels that were within reference range. In conclusion, GFAP may be useful as an additional disease biomarker in patients with narcolepsy, and this hypothesis should be investigated in larger studies. PMID:23746601
One of the major challenges in management of spinal cord injury (SCI) is that the assessment of injury severity is often imprecise. Identification of reliable, easily quantifiable biomarkers that delineate the severity of the initial injury and that have prognostic value for the degree of functional recovery would significantly aid the clinician in the choice of potential treatments. To find such biomarkers we performed quantitative liquid chromatography-mass spectrometry (LC-MS/MS) analyses of cerebrospinalfluid (CSF) collected from rats 24 h after either a moderate or severe SCI. We identified a panel of 42 putative biomarkers of SCI, 10 of which represent potential biomarkers of SCI severity. Three of the candidate biomarkers, Ywhaz, Itih4, and Gpx3 were also validated by Western blot in a biological replicate of the injury. The putative biomarkers identified in this study may potentially be a valuable tool in the assessment of the extent of spinal cord damage.
Lubieniecka, Joanna M.; Streijger, Femke; Lee, Jae H. T.; Stoynov, Nikolay; Liu, Jie; Mottus, Randy; Pfeifer, Tom; Kwon, Brian K.; Coorssen, Jens R.; Foster, Leonard J.; Grigliatti, Thomas A.; Tetzlaff, Wolfram
Acetazolamide (ACTZ), a carbonic anhydrase inhibitor, has been shown to decrease cerebrospinalfluid (CSF) production in both in vivo and in vitro animal models. We report two children with hydrocephalus who experienced multiple shunt failures, and who had externalised ventriculostomy drains (EVD) prior to ventriculopleural shunt placement. The effects of increasing doses of ACTZ on CSF production and subsequent tolerance to ventriculopleural shunts were evaluated. The patients had a 48% and a 39% decrease in their EVD CSF output when compared to baseline with maximum ACTZ dose of 75 mg/kg/day and 50 mg/kg/day, respectively (p < 0.05). This is the first report of change in CSF volume in children after extended treatment with ACTZ. ACTZ treatment in mechanically ventilated paediatric patients with hydrocephalus may improve tolerance of ventriculopleural shunts and minimise respiratory compromise. Potassium and bicarbonate supplements are required to correct metabolic disturbances. PMID:11124792
Carrion, E; Hertzog, J H; Medlock, M D; Hauser, G J; Dalton, H J
Spontaneous cerebrospinalfluid (CSF) otorrhea is defined as CSF otorrhea where there are no identifiable causes including previous trauma, surgery, infection, neoplasm or congenital anomaly. The condition is rare. The origin of CSF leak is commonly a defect in the tegmen of the middle cranial fossa. The pathophysiology of spontaneous CSF otorrhea is unclear. Two theories of the etiology of bony defects of the temporal bone are the congenital bony defect theory and arachnoid granulation theory. The authors experienced a case of a 49-year-old female patient admitted with the complaint of persistent right ear fullness. Computed tomography revealed a large defect of the middle fossa and suspicious CSF otorrhea through the defect of tegmen tympani. Repair was successful with multiple bone chips using the transmastoid approach. The postoperative course was good and there has been no recurrence of the CSF leakage. PMID:24653924
Although universally recognized as the source of cerebrospinalfluid (CSF), the choroid plexus (ChP) has been one of the most understudied tissues in neuroscience. The reasons for this are multiple and varied, including historical perceptions about passive and permissive roles for the ChP, experimental issues, and lack of clinical salience. However, recent work on the ChP and instructive signals in the CSF have sparked new hypotheses about how the ChP and CSF provide unexpected means for regulating nervous system structure and function in health and disease, as well as new ChP-based therapeutic approaches using pluripotent stem cell technology. This minisymposium combines new and established investigators to capture some of the newfound excitement surrounding the ChP-CSF system.
Bjornsson, Christopher S.; Dymecki, Susan M.; Gilbertson, Richard J.; Holtzman, David M.
Tau protein in cerebrospinalfluid (CSF) is an important biomarker of Alzheimer's disease and some other brain diseases. Enzyme-linked immunosorbent assays (ELISAs) have been mostly used for quantification of tau and other biomarkers in CSF. However, these assays do not have sufficient sensitivity and dynamic range. In this study we tested the suitability of gold nanoparticles functionalized with tau-specific monoclonal antibody and oligonucleotide template for immuno-polymerase chain reaction (Nano-iPCR) quantification of tau protein in human CSF samples and compared it with ELISA, either commercial or newly developed with tyramide signal amplification. Our data indicate that Nano-iPCR is superior in sensitivity and detection range to ELISA in tau protein detection. PMID:24642424
Infusions of artificial cerebrospinalfluid (CSF) into the cerebroventricles of conscious rats can raise CSF pressure (CSFp). This response can be modified by some neuropeptides. One of these, angiotensin, facilitates the rise in CSFp. We measured CSFp in conscious rats with a computerized system and evaluated resistance to CSF outflow during infusion of artificial CSF, with or without angiotensin, from the decay kinetics of superimposed bolus injections. Angiotensin (10 ng/min) raised CSFp (P less than 0.05) compared with solvent, but the resistance to CSF outflow of the two groups was similar (P greater than 0.05). Because CSFp was increased by angiotensin without an increase in the outflow resistance, a change in some volume compartment is likely. Angiotensin may raise CSFp by increasing CSF synthesis; this possibility is supported, since the choroid plexuses contain an intrinsic isorenin-angiotensin system. Alternatively, angiotensin may dilate pial arteries, leading to an increased intracranial blood volume.
Increased trans-lamina cribrosa pressure difference (TLCPD), the difference of intraocular pressure (IOP) and orbital cerebrospinalfluid pressure (CSF-P), has been investigated as a possible risk factor in glaucoma pathogenesis. In fact, lower CSF-P in the setting of normal IOP has been implicated as a potential risk factor for normal tension glaucoma. Increased TLCPD has been associated with decreased neuroretinal rim area and increased visual field defects. Furthermore, dysregulation of systemic blood pressure has been associated with changes in IOP. Recent studies have also suggested that increased body mass index (BMI) is associated with decreased prevalence of glaucoma, which may be due to an increased CSF-P with increased BMI found in many studies. Given the interaction of various pressures, their role in glaucoma pathophysiology has come under investigation and warrants further study in order to better understand the aetiology and progression of glaucoma. PMID:24307714
A 65-year-old man with sudden back pain was transferred to our hospital by ambulance, who also complained of sensory and motor disorder of bilateral legs on arrival. The neurological disorder was gradually aggravated and paraplegia below the level of Th10 was manifested. Computed tomography demonstrated DeBakey IIIb acute aortic dissection; therefore, the paraplegia was thought to be due to spinal cord ischemia caused by the acute aortic dissection. Emergent cerebrospinalfluid drainage was performed, and it was very effective for the relief from paraplegia. The hospital course after the drainage was uneventful and he was discharged on the 39th day after the onset of symptoms. PMID:23555433
ABSTRACT Acute central nervous system (CNS) infections cause substantial morbidity and mortality, but the etiology remains unknown in a large proportion of cases. We identified and characterized the full genome of a novel cyclovirus (tentatively named cyclovirus-Vietnam [CyCV-VN]) in cerebrospinalfluid (CSF) specimens of two Vietnamese patients with CNS infections of unknown etiology. CyCV-VN was subsequently detected in 4% of 642 CSF specimens from Vietnamese patients with suspected CNS infections and none of 122 CSFs from patients with noninfectious neurological disorders. Detection rates were similar in patients with CNS infections of unknown etiology and those in whom other pathogens were detected. A similar detection rate in feces from healthy children suggested food-borne or orofecal transmission routes, while high detection rates in feces from pigs and poultry (average, 58%) suggested the existence of animal reservoirs for such transmission. Further research is needed to address the epidemiology and pathogenicity of this novel, potentially zoonotic virus.
Tan, Le Van; van Doorn, H. Rogier; Nghia, Ho Dang Trung; Chau, Tran Thi Hong; Tu, Le Thi Phuong; de Vries, Michel; Canuti, Marta; Deijs, Martin; Jebbink, Maarten F.; Baker, Stephen; Bryant, Juliet E.; Tham, Nguyen Thi; BKrong, Nguyen Thi Thuy Chinh; Boni, Maciej F.; Loi, Tran Quoc; Phuong, Le Thi; Verhoeven, Joost T. P.; Crusat, Martin; Jeeninga, Rienk E.; Schultsz, Constance; Chau, Nguyen Van Vinh; Hien, Tran Tinh; van der Hoek, Lia; Farrar, Jeremy; de Jong, Menno D.
To a certain extent, the cerebrospinalfluid (CSF) composition reflects the current status of the central nervous system (CNS). Therefore, studying changes in even the most essential CSF parameters provides enormous scope for obtaining valuable information about processes in the CNS in relation to its disorders. The article aims at presenting our current conception of urgent CSF examination with special emphasis on early diagnosis of central nervous infections. In particular, the focus is on evaluating energy conditions in the CSF compartment and permeability of the blood-brain and blood-CSF barriers, CSF cytology, detecting CNS tissue destruction and bleeding into CNS pathways and monitoring the levels of systemic inflammatory activity. PMID:17417750
The involvement of the neuropeptides oxytocin (OXT) and vasopressin (AVP) in human socio-emotional behaviours is attracting increasing attention. There is ample evidence for elevated plasma levels upon a wide variety of social and emotional stimuli and scenarios, ranging from romantic love via marital distress up to psychopathology, with cause versus consequence being largely unclear. The present study examined whether plasma levels of both OXT and AVP are reflective of central neuropeptide levels, as assumed to impact upon socio-emotional behaviours. Concomitant plasma and cerebrospinalfluid (CSF) samples were taken from 41 non-neurological and nonpsychiatric patients under basal conditions. Although OXT and AVP levels in the CSF exceeded those in plasma, there was no correlation between both compartments, clearly suggesting that plasma OXT and AVP do not predict central neuropeptide concentrations. Thus, the validity of plasma OXT and AVP as potential biomarkers of human behaviour needs further clarification. PMID:23574490
Kagerbauer, S M; Martin, J; Schuster, T; Blobner, M; Kochs, E F; Landgraf, R
The cerebrospinalfluid drawn from the fourth ventricles of the brains of cats during and after the development of motion sickness was studied to determine what neurotransmitters may be involved in the development of the sickness. The analytical procedure, which uses HPLC coupled with n-electrode coulometric electrochemical detection to measure many compounds with picogram sensitivity, is described. Baseline levels of DOPAC, MHPGSO4, uric acid, DA, 5-HIAA, and HVA were lower on motion and control days in cats which became motion sick when compared with cats which did not. None of the total of 36 identified compounds identified in the samples varied as a function of either exposure to motion or provocation of emesis. It is concluded that susceptibility to motion sickness is a manifestation of individual differences related to fundamental neurochemical composition.
Lucot, James B.; Crampton, George H.; Matson, Wayne R.; Gamache, Paul H.
Oligomers of the amyloid beta-protein (Abeta) play an important role in Alzheimer's disease (AD). We hypothesized that AD patients have a central nervous system environment that promotes Abeta oligomerization. We investigated the effect of cerebrospinalfluid (CSF) from 33 patients with AD and 33 age-matched, non-demented controls on oligomerization of Abeta1-40 and Abeta1-42 using the technique of photo-induced cross-linking of unmodified proteins. CSF inhibited oligomerization of both Abeta1-40 and Abeta1-42. This inhibitory effect was significantly weaker in AD patients than in non-demented controls. Our results indicate that AD patients have a CSF environment favorable for Abeta oligomerization. PMID:20413863
Ikeda, Tokuhei; Ono, Kenjiro; Elashoff, David; Condron, Margaret M; Noguchi-Shinohara, Moeko; Yoshita, Mitsuhiro; Teplow, David B; Yamada, Masahito
To study biochemical changes in cerebrospinalfluid (CSF), we developed a reliable technique for repeated collection of CSF in anesthetized strain 13 guinea pigs. The animal's head was mounted in a stereotaxic instrument with ventral tilt at 30 degrees, and cisternal puncture was made with an L-shaped, 23-gauge needle through the shaved skin. Clear CSF was collected in a 1-ml syringe surrounded by crushed ice. Each collection procedure lasted for 3 min, and three consecutive collections produced about 0.2 ml of CSF. Sampling was repeated at 3-hr intervals. With intravenous saline infusion (10 ml/kg.hr), a total volume of 0.6-1.0 ml of CSF was collected over 6 to 12 hr. Animals maintained a mean blood pressure, heart rate, and minute volume, with few changes during CSF sampling for the entire collection. PMID:1871150
Cortical development depends on the active integration of cell autonomous and extrinsic cues, but the coordination of these processes is poorly understood. Here, we show that the apical complex protein Pals1 and Pten have opposing roles in localizing the Igf1R to the apical, ventricular domain of cerebral cortical progenitor cells. We found that the cerebrospinalfluid (CSF), which contacts this apical domain, has an age-dependent effect on proliferation, much of which is attributable to Igf2, but that CSF contains other signaling activities as well. CSF samples from patients with glioblastoma multiforme show elevated Igf2 and stimulate stem cell proliferation in an Igf2-dependent manner. Together, our findings demonstrate that the apical complex couples intrinsic and extrinsic signaling, enabling progenitors to sense and respond appropriately to diffusible CSF-borne signals distributed widely throughout the brain. The temporal control of CSF composition may have critical relevance to normal development and neuropathological conditions.
Lehtinen, Maria K.; Zappaterra, Mauro W.; Chen, Xi; Yang, Yawei J.; Hill, Anthony; Lun, Melody; Maynard, Thomas; Gonzalez, Dilenny; Kim, Seonhee; Ye, Ping; D'Ercole, A. Joseph; Wong, Eric T.; LaMantia, Anthony S.; Walsh, Christopher A.
Aseptic meningitis refers to a clinical syndrome of meningeal inflammation in which bacteria cannot be identified in the cerebrospinalfluid (CSF). The viral etiology and the epidemiological, clinical, and laboratory characteristics of aseptic meningitis among children aged 2 months to 15 years in Shiraz, southern Iran were determined. From May 2007 to April 2008, 65 patients were admitted to the hospital with aseptic meningitis. Seven viruses, non-polio human enteroviruses, mumps virus, herpes simplex virus (HSV), varicella-zoster virus (VZV), human cytomegalovirus (HCMV), human herpes virus type 6 (HHV-6), and Epstein-Barr virus (EBV) were investigated by polymerase chain reaction (PCR) method. Viruses were detected in 30 (46.2%) patients in whom non-polio human enterovirus and mumps virus were detected in 13 (43.3%) and 11 (36.7%), respectively. The remaining 6 (20%) of the cases were caused by HSV, VZV, HCMV, and HHV-6. Haemophilus influenzae and non-polio human enterovirus were detected in one patient simultaneously. Viral meningitis was found to be more frequent during spring and summer. The majority (66.6%) of the patients were treated in the hospital for 10 days and had received antibiotics in the case of bacterial meningitis. Rapid diagnosis of viral meningitis using PCR testing of CSF can help shorten hospitalization, and avoid the unnecessary use of antibiotics. PMID:21412795
Study Objectives: The possible relationship between cerebrospinalfluid (CSF) hypocretin and leptin levels, overweight, and association to risk factors for diabetes 2 in narcolepsy with cataplexy were compared to patients with idiopathic hypersomnia and controls. Patients: 26 patients with narcolepsy, cataplexy, and hypocretin deficiency; 23 patients with narcolepsy, cataplexy, and normal hypocretin values; 11 patients with idiopathic hypersomnia; and 43 controls. Measurements and Results: Body mass index (BMI), serum leptin, and HbA1C were measured in patients and controls; and CSF hypocretin 1 and leptin measured in all patients. Female and male patients with narcolepsy and hypocretin deficiency had the highest mean BMI (27.8 and 26.2, respectively), not statistically different from patients with narcolepsy and normal hypocretin or controls, but statistically higher than the patients with idiopathic hypersomnia (p < 0.001 and 0.011, respectively). The number of obese patients (BMI > 30) was increased in both narcolepsy groups. Serum and CSF leptin levels correlated positively to BMI in patients and controls, but not to CSF hypocretin concentrations. HbA1C was within normal levels and similar in all groups. Conclusions: The study confirms a moderate tendency to obesity (BMI > 30) and overweight in patients with narcolepsy and cataplexy. Obesity was not correlated to hypocretin deficiency or reduced serum or CSF leptin concentrations. We suggest that overweight and possible metabolic changes previously reported in narcolepsy, may be caused by other mechanisms. Citation: Heier MS; Jansson TS; Gautvik KM. Cerebrospinalfluid hypocretin 1 deficiency, overweight, and metabolic dysregulation in patients with narcolepsy. J Clin Sleep Med 2011;7(6):653-658.
Heier, Mona S.; Jansson, Tine S.; Gautvik, Kaare M.
Assays capable of concurrently measuring small quantities of noradrenaline, dopamine, serotonin, and several of their metabolites in cerebrospinalfluid (c.s.f.) were developed by the use of high performance liquid chromatography with electrochemical detection. For comparison, cortical subarachnoid, ventricular, cisternal and lumbar c.s.f. were obtained by puncture under barbiturate anaesthesia in sheep. Basal concentrations related to the adrenergic system, including methoxyhydroxyphenylglycol (MHPG), were similar in ventricular, cisternal and lumbar c.s.f., and those of the serotoninergic metabolites, 5-hydroxyindole-3-acetylacetic acid (5-HIAA), were similar in ventricular and cisternal c.s.f. High concentrations of the dopamine metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were found only in ventricular c.s.f. Monoamine metabolites in ventricular c.s.f. under basal conditions and after various experimental manipulations were then determined over periods of 3 months in two different breeds of sheep fitted chronically with cannulae in lateral ventricles. A dose-related accumulation of all the acidic monoamine metabolites was recorded during treatment with probenecid. The increase in 5-HIAA was linear after administration of increased doses of tryptophan and 5-hydroxytryptophan. The concentrations of dopamine, DOPAC and HVA in the ventricular c.s.f. reflected the response of the dopaminergic system to agents capable of crossing the blood-brain barrier. It is concluded that cerebral metabolism in conscious sheep could be indirectly approached by recording the concentration of end-products of dopamine metabolism in ventricular cerebrospinalfluid, obtained under conditions of minimal stress.
Complete concentration-time data describing the pharmacokinetics of fluconazole in the cerebrospinalfluid (CSF) following a single dose are not available for humans or animals. We studied the pharmacokinetics of fluconazole with an indwelling intracisternal needle as described by R.G. Dacey and M.A. Sande (Antimicrob. Agents Chemother. 6:437-441, 1974). To determine whether the presence of an intracisternal needle alters pharmacokinetics in the CSF, we validated this model with uninfected rabbits by measuring pharmacokinetic constants following direct intracisternal and intravenous administration of fluconazole. Following direct injection, there was no alteration of elimination rates in the CSF with increasing sample number or time. Following intravenous administration, the penetration and kinetic constants were the same in individual animals from which multiple CSF samples were obtained as in a composite subject constructed by pooling virgin samples from different animals. The presence of the intracisternal needle did not alter CSF chemistry or leukocyte counts, and erythrocyte contamination was < 0.001%. While drug concentrations were measured by a microbiological assay, we also compared the sensitivity and reproducibility of a high-performance liquid chromatography (HPLC) assay with those of the microbiological assay. Following a single intravenous dose, the maximum concentration of the drug in serum, the time to maximum concentration of the drug in serum, the terminal elimination half-life in the CSF, and the percent penetration by fluconazole were 6.12 micrograms/ml, 1 h, 9.0 h, and 84.3%, respectively. We conclude that the sampling of CSF via an indwelling needle does not alter fluconazole pharmacokinetics, cause inflammation, or alter chemical parameters; that the microbiological assay is at least equivalent in sensitivity and reproducibility to the HPLC assay; and that robust parameters describing the pharmacokinetics of fluconazole are possible with this model.
Madu, A; Cioffe, C; Mian, U; Burroughs, M; Tuomanen, E; Mayers, M; Schwartz, E; Miller, M
Neurological outcomes of preterm infants with posthemorrhagic hydrocephalus are among the worst in newborn medicine. There remains no consensus regarding the diagnosis or treatment of posthemorrhagic hydrocephalus, and the pathological pathways leading to the adverse neurological sequelae are poorly understood. In the current study, we developed an innovative approach to simultaneously identify potential diagnostic markers of posthemorrhagic hydrocephalus and investigate novel pathways of posthemorrhagic hydrocephalus-related neurological disability. Tandem multi-affinity fractionation for specific removal of plasma proteins from the hemorrhagic cerebrospinalfluid samples was combined with high resolution label-free quantitative proteomics. Analysis of cerebrospinalfluid obtained from infants with posthemorrhagic hydrocephalus demonstrated marked differences in the levels of 438 proteins when compared with cerebrospinalfluid from age-matched control infants. Amyloid precursor protein, neural cell adhesion molecule-L1, neural cell adhesion molecule-1, brevican and other proteins with important roles in neurodevelopment showed profound elevations in posthemorrhagic hydrocephalus cerebrospinalfluid compared with control. Initiation of neurosurgical treatment of posthemorrhagic hydrocephalus resulted in resolution of these elevations. The results from this foundational study demonstrate the significant promise of tandem multi-affinity fractionation-proteomics in the identification and quantitation of protein mediators of neurodevelopment and neurological injury. More specifically, our results suggest that cerebrospinalfluid levels of proteins such as amyloid precursor protein or neural cell adhesion molecule-L1 should be investigated as potential diagnostic markers of posthemorrhagic hydrocephalus. Notably, dysregulation of the levels these and other proteins may directly affect ongoing neurodevelopmental processes in these preterm infants, providing an entirely new hypothesis for the developmental disability associated with posthemorrhagic hydrocephalus.
Morales, Diego M.; Townsend, R. Reid; Malone, James P.; Ewersmann, Carissa A.; Macy, Elizabeth M.; Inder, Terrie E.; Limbrick, David D.
We describe a rapid and sensitive method for the quantification of homocarnosine in physiological fluids, with particular emphasis on cerebrospinalfluid (CSF). Homocarnosine was quantified as the butyl derivative, with 2H2-l-homocarnosine as internal standard. Following deproteinization of CSF samples, supernatants were evaporated to dryness and derivatized with 10% 6M HCl in butanol. Samples were chromatographed on a C18 column and
Erwin E. W. Jansen; K. Michael Gibson; Yosuke Shigematsu; Cornelis Jakobs; Nanda M. Verhoeven
The patient is a healthy 11-year-old girl with no history of trauma or hearing impairment. She developed pneumococcal meningitis three times, at ages 7, 10, and 11. Intracranial examination revealed, pore expansion and cerebrospinalfluid leakage in the right internal acoustic foramen, which were attributed to a bone malformation of the base of the skull. A procedure was performed to close the cerebrospinalfluid leakage; no relapse has been observed thus far. Previous case reports indicate that repetitive bacterial meningitis is often caused by internal ear malformation, trauma, tumors, or surgical operation. This case suggests the possibility that underlying disorders may not be apparent in cases of repetitive bacterial meningitis and, more proactive investigations are required to prevent further recurrence of meningitis. PMID:24084029
We have conducted an in vitro coagulation study consisting of two separate groups of 20 subjects using the thrombelastograph. In the first group, haemodilution was performed with a physiological balanced salt solution similar to plasma, with the exception of calcium, and buffered to a normal pH (Plasmalyte B) at 37 degrees C on blood obtained from consenting volunteers. In the second group, a protein-poor body fluid (cerebrospinalfluid (CSF)) obtained from parturient patients undergoing spinal anaesthesia for Caesarean section was used as the diluent. There were statistically significant differences between the warmed Plasmalyte B treated samples and their untreated controls for all variables measured by the thrombelastograph, except for maximum amplitude, and between the CSF treated samples and their untreated controls for all variables. We conclude that electrolyte and acid-base composition of the diluent fluid had no effect on the observation that crystalloid haemodilution produces hypercoagulability. The marked increase in coagulability produced by addition of CSF cannot be explained on a simple haemodilution basis and confirms previous suggestions of the presence of a procoagulant factor in CSF. PMID:10325846
The Limulus amoebocyte lysate endotoxin assay was evaluated as a method for rapid diagnosis of acute bacterial meningitis in a series of 305 patients. The results of Limulus assays on cerebrospinalfluid (CSF) samples from these patients were compared with the results for each patient of routine bacterial cultures and Gram stains. Positive Limulus tests were obtained on initial CSF specimens from 84% of patients with culture-proven bacterial meningitis, including all patients with meningitis due to gram-negative organisms. Initial Gram-stained smears revealed the presence of organisms in 68% of the patients. One patient with pneumococcal meningitis had a weakly positive Limulus assay, whereas patients with meningitis due to other gram-positive organisms, those with aseptic meningitis, or patients without meningitis had negative CSF Limulus tests. The Limulus assay also demonstrated the persistence of endotoxin in the CSF of certain patients during antibiotic therapy, especially patients with Haemophilus influenzae meningitis. The Limulus test proved to be a rapid, reliable indicator of the presence of gram-negative organisms in the CSF of patients suspected of acute bacterial meningitis.
The development of Alzheimer's disease (AD) biomarkers remains an unmet challenge, and new approaches that can improve current AD biomarker strategies are needed. Recent reports suggested that microRNA (miRNA) profiling of biological fluids has emerged as a diagnostic tool for several pathologic conditions. In this study, we measured six candidate miRNAs (miR-9, miR-29a, miR-29b, miR-34a, miR-125b, and miR-146a) in plasma and cerebrospinalfluid (CSF) of AD and normal subjects by using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) to evaluate their potential usability as AD biomarkers. The qRT-PCR results showed that plasma miR-34a and miR-146a levels, and CSF miR-34a, miR-125b, and miR-146a levels in AD patients were significantly lower than in control subjects. On the other hand, CSF miR-29a and miR-29b levels were significantly higher than in control subjects. Our results provide a possibility that miRNAs detected in plasma and CSF can serve as biomarkers for AD. PMID:24157723
Our work aims to develop a biomechanical model of hydrocephalus both intended to perform clinical research and to assist the neurosurgeon in diagnosis decisions. Recently, we have defined a new MR imaging sequence based on SPACE (Sampling Perfection with Application optimized Contrast using different flip-angle Evolution). On these images, the cerebrospinalfluid (CSF) appears as a homogeneous hypersignal. Therefore such images are suitable for segmentation and for volume assessment of the CSF. In this paper we present a fully automatic 3D segmentation of such SPACE MRI sequences. We choose a topological approach considering that CSF can be modeled as a simply connected object (i.e. a filled sphere). First an initial object which must be strictly included in the CSF and homotopic to a filled sphere, is determined by using a moment-preserving thresholding. Then a priority function based on an Euclidean distance map is computed in order to control the thickening process that adds "simple points" to the initial thresholded object. A point is called simple if its addition or its suppression does not result in change of topology neither for the object, nor for the background. The method is validated by measuring fluid volume of brain phantoms and by comparing our volume assessments on clinical data to those derived from a segmentation controlled by expert physicians. Then we show that a distinction between pathological cases and healthy adult people can be achieved by a linear discriminant analysis on volumes of the ventricular and intracranial subarachnoid spaces.
The function of cerebrospinalfluid (CSF) is to protect the brain and optic nerve from mechanical damage, provide nutrition for axons/neurons, and remove of toxic metabilites. CSF is produced mainly by the choroid plexus epithelium and ependymal cells of the ventricles and flows into interconnecting chambers; namely, the cisterns and the subarachnoid spaces. Based on studies of CSF circulation and direction of flow using radioisotopes and other tracers injected into the CSF, it is thought that there is a bulk circulation of fluid from the sites of production in the third, fourth, and lateral ventricles to the arachnoid villi and probably to the lymphatic capillaries in the cranial dura mater. The mechanism by which CSF is propelled is incompletely understood, but probably is influenced by the release of newly produced CSF, ventricular pulsations, and the pulse pressure of the vascular choroid plexus. This mechanism would account for the steady CSF pressure. In addition to the steady CSF pressure, overlapping pressure spikes occur during trunk inclination, coughing and other valsalva. PMID:23733131
Background Highly abundant proteins in biological fluids such as serum or cerebrospinalfluid (CSF) can hinder the detection of proteins in lower abundance, e.g., potential biomarkers. Commercial products are available for the depletion of albumin and immunoglobulins (Igs), although most of these kits have not been validated for dog samples. The present study therefore examines the use of different types of depletion kits for dog CSF. Findings Three kits, with different mechanisms for the depletion of albumin and Igs, were tested with dog CSF specimens. One product significantly decreased the amount of albumin; with all kits, IgG was less efficiently removed than albumin. Mass spectrometry of the fractions eluted from the depletion columns revealed considerable co-depletion of other CSF proteins. Conclusions A commercially available depletion kit was identified which depletes albumin and (to a lower extent) immunoglobulins from dog CSF. However, the limited efficacy and the concomitant loss of other proteins from the sample should be taken into account when using this product.
An 18-year-old woman presented with a progressively worsening headache, photophobia feverishness and vomiting. Three weeks previously she had returned to the UK from a trip to Peru. At presentation, she had clinical signs of meningism. On admission, blood tests showed a mild lymphopenia, with a normal C reactive protein and white cell count. Chest X-ray and CT of the head were normal. Cerebrospinalfluid (CSF) microscopy was normal. CSF protein and glucose were in the normal range. MRI of the head and cerebral angiography were also normal. Subsequent molecular testing of CSF detected enterovirus RNA by reverse transcriptase PCR. The patient's clinical syndrome correlated with her virological diagnosis and no other cause of her symptoms was found. Her symptoms were self-limiting and improved with supportive management. This case illustrates an important example of viral central nervous system infection presenting clinically as meningitis but with normal CSF microscopy. PMID:25035443
Dawood, Naghum; Desjobert, Edouard; Lumley, Janine; Webster, Daniel; Jacobs, Michael
Angiostrongylus cantonensis produces eosinophilic meningitis in humans and is endemic in Thailand, Taiwan, China, and the Caribbean region. During infection with this parasite, it is important to know if the complement system may be activated by the classical or lectin pathway. Cerebrospinalfluid and serum samples from 20 patients with meningitic angiostrongyliasis were used to quantify C4 levels and albumin. Results were plotted on a C4 CSF/serum quotient diagram or Reibergram. Twelve patients showed intrathecal synthesis of C4. Antibody-dependent complement cytotoxicity should be considered as a possible mechanism that destroys third-stage larvae of this helminth in cerebrospinalfluid of affected patients.
Padilla-Docal, Barbara; Dorta-Contreras, Alberto Juan; Bu-Coifiu-Fanego, Raisa; Rodriguez-Rey, Alexis; Gutierrez-Hernandez, Juan Carlos; de Paula-Almeida, Susana Olga
Multiple sclerosis is a neurological disorder that presents with symptoms including inflammation, neurodegeneration, and demyelination of the central nervous system (CNS). Secondary progressive multiple sclerosis (SPMS) manifests with serious physical disability. To quantitatively analyze differential protein expression in patients with SPMS, we performed two-dimensional fluorescence difference in-gel electrophoresis, followed by mass spectrometry on the cerebrospinalfluid of these patients and patients with other neurological diseases. Vitamin D-binding protein (DBP), gelsolin, albumin, etc. showed more than a 1.5-fold difference between the two groups. Based on these results, an experimental allergic encephalomyelitis (EAE) model of multiple sclerosis in Lewis rats was used to investigate DBP's role in the disease. Protein levels, mRNA transcripts, and ligands of DBP in different regions of the CNS were evaluated under various vitamin D intake levels. Here, DBP levels increased in the experimental rat groups compared to the control groups regardless of vitamin D intake. Moreover, DBP mRNA levels varied in different parts of the CNS including spinal cords in the experimental groups. The observed differences between DBP protein and mRNA levels in the experimental groups' spinal cords could be derived from the disruption of the blood-brain barrier. Furthermore, an interaction between DBP and actin was confirmed using coimmunoprecipitation and western blot. These results indicate a role for DBP in the actin scavenge system. Moreover, in the experimental group that received oral vitamin D3 supplement, we observed both delayed onset and diminished severity of the disease. When DBP was upregulated, however, the benefits from the vitamin D3 supplements were lost. Thus, we inferred that high levels of DBP were adverse to recovery. In conclusion, here we observed upregulated DBP in the cerebrospinalfluid could serve as a specific diagnostic biomarker for the progression of multiple sclerosis. Next, we demonstrate the vital function of increased levels of free vitamin D metabolites for multiple sclerosis treatment. Finally, vitamin D supplements may be particularly beneficial for SPMS patients. PMID:23339019
Purpose To examine potential associations between body height, cerebrospinalfluid pressure (CSFP), trans-lamina cribrosa pressure difference (TLCPD) and prevalence of open-angle glaucoma (OAG) in a population-based setting. Methods The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years (range:50–93 years). A detailed ophthalmic examination was performed. Based on a previous study with lumbar cerebrospinalfluid pressure (CSFP) measurements, CSFP was calculated as CSFP[mmHg]?=?0.44×Body Mass Index[kg/m2]+0.16×Diastolic Blood Pressure[mmHg]-0.18×Age[Years]-1.91 Results Data of IOP and CSFP were available for 3353 (96.7%) subjects. Taller body height was associated with higher CSFP (P<0.001; standardized correlation coefficient beta:0.13; regression coefficient B:0.29; 95% confidence interval (CI):0.25,0.33) after adjusting for male gender, urban region of habitation, higher educational level, and pulse rate. If TLCPD instead of CSFP was added, taller body height was associated with lower TLCPD (P<0.001;beta:?0.10;B:?0.20;95%CI:?0.25,?0.15). Correspondingly, higher CSFP was associated with taller body height (P?=?0.003;beta:0.02;B:0.01;95%CI:0.00,0.02), after adjusting for age, gender, body mass index, pulse, systolic blood pressure, and blood concentration of cholesterol. If IOP was added to the model, higher CSFP was associated with higher IOP (P<0.001;beta:0.02;B:0.02;95%CI:0.01,0.03). TLCPD was associated with lower body height (P?=?0.003;beta:?0.04;B ?0.02,95%CI:?0.04,?0.01) after adjusting for age, body mass index, systolic blood pressure, pulse, blood concentrations of triglycerides, axial length, central corneal thickness, corneal curvature radius, and anterior chamber depth. Adding the prevalence of OAG to the multivariate analysis revealed, that taller body height was associated with a lower OAG prevalence (P?=?0.03;beta:?0.03;B:?1.20;95%CI:?2.28,?0.12) after adjusting for educational level and gender. Conclusions Taller body height was associated with higher CSFP and lower TLCPD (and vice versa), after adjusting for systemic and ocular parameters. Parallel to the associations between a higher prevalence of glaucoma with a lower CSFP or higher TLCPD, taller body height was associated with a lower prevalence of OAG.
Alterations of the intracellular ubiquitin-proteasome pathway are found in neurodegenerative and inflammatory disorders of the central nervous system, as well as in its malignancies. Inhibitory substrates of the proteasomes represent promising approaches to control autoimmune inflammations and induction of apoptosis in cancer cells. Extracellular circulating proteasomes are positively correlated to outcome prognosis in hematogenic neoplasias and the outcome in critically ill patients. Previously, we reported raised levels of proteolytic active 20S proteasomes in the extracellular alveolar space in patients with acute respiratory distress syndrome (ARDS). For the cerebrospinalfluid, we assumed that extracellular circulating proteasomes with enzymatic activity can be found, too. Cerebrospinalfluid (CSF) samples of twenty-six patients (14 females, 12 males), who underwent diagnostic spinal myelography, were analyzed for leukocyte cell count, total protein content, lactate and interleukine-6 (Il-6) concentrations. CSF samples were analyzed for concentration and enzymatic activity of extracellular 20S proteasomes (fluorescenic substrate cleavage; femtokatal). Blood samples were analyzed with respect to concentration of extracellular circulating proteasomes. Choroidal plexus was harvested at autopsies and examined with immunoelectron microscopy (EM) for identification of possible transportation mechanisms. Statistical analysis was performed using SPSS (18.0.3). In all patients, extracellular proteasome was found in the CSF. The mean concentration was 24.6 ng/ml. Enzymatic activity of the 20S subunits of proteasomes was positively identified by the fluorescenic subtrate cleavage at a mean of 8.5 fkat/ml. Concentrations of extracellular proteasomes in the CSF, total protein content and Il-6 were uncorrelated. Immunoelectron microscopy revealed merging vesicles of proteasomes with the outer cell membrane suggestive of an exozytic transport mechanism. For the first time, extracellular circulating 20S proteasome in the CSF of healthy individuals is identified and its enzymatic activity detected. A possible exozytic vesicle-bond transportation mechanism is suggested by immunoelectron microscopy. The present study raises more questions on the function of extracellular proteasome in the CSF and encourages further studies on the role of extracellular protesomes in pathological conditions of the central nervous system (tumor lesions and inflammatory processes). PMID:21881828
Unanesthetized adult female ponies were studied near sea level (250 m) and during sojourns to 3400 m (N=6) and 4300 m (N=7) altitude. The pH, PCO2, and PO2 of arterial blood and pH and PCO2 of cerebrospinalfluid (CSF) were measured under conditions of acute (1 hr) and chronic (1-45 days) hypoxia. Cerebrospinalfluid was sampled from the cisterna magna of the awake pony and arterial blood withdrawn from an indwelling arterial catheter. In both groups of animals, PaCO2 decreased slightly after 1 hr of hypoxia (delta PaCO2= - 0.6 mm Hg at 3400 m; - 3.9 mm Hg at 4300 m), decreased further after 1-5 days at high altitude (delta PaCO2= - 7.2 mm Hg at 3400 m; - 12.3 mm Hg at 4300 m) and then increased significantly after 6 days of chronic hypoxia (delta PaCO2= + 4.1 mm Hg at 3400 m; + 4.7 mm Hg at 4300 m). Although PaO2 decreased markedly during acute hypoxia, subsequent changes in PaCO2 at high altitude did not alter PaO2 from that observed during acute hypoxia (PaO2=52 mm Hg at 3400 m; 41 mm Hg at 4300 m). The pH of CSF increased during acute hypoxia (delta pH= + 0.013 unit at 3400 m; + 0.033 unit at 4300 m) and became more alkaline after 1-2 days at high altitude (delta pH= + 0.031 unit at 3400 m; + 0.064 unit at 4300 m). At 4300 m, CSF pH remained alkaline to control values throughout sojourn. Under these conditions of chronic hypocapnic hypoxia, CSF pH was imperfectly regulated and regulated in a magnitude equal to (3400 m) or less than (4300 m) arterial blood. Furthermore, the similarity of relative changes in CSF [HCO3-] and arterial [HCO3-] during chronic hypoxia may indicate a passive regulation of CSF [HCO3-] rather than local 'CSF-specific' mechanisms as previously proposed. PMID:241107
Orr, J A; Bisgard, G E; Forster, H V; Buss, D D; Dempsey, J A; Will, J A
Danger-associated molecular patterns (DAMPs) are nuclear or cytoplasmic proteins that are released from the injured tissues and activate the innate immune system. Mitochondrial DNA (mtDNA) is a novel DAMP that is released into the extracellular milieu subsequent to cell death and injury. We hypothesized that cell death within the central nervous system in children with traumatic brain injury (TBI) would lead to the release of mtDNA into the cerebrospinalfluid (CSF) and has the potential to predict the outcome after trauma. Cerebrospinalfluid was collected from children with severe TBI who required intracranial pressure monitoring with Glasgow Coma Scale (GCS) scores of 8 or less via an externalized ventricular drain. Control CSF was obtained in children without TBI or meningoencephalitis who demonstrated no leukocytes in the diagnostic lumbar puncture. The median age for patients with TBI was 6.3 years, and 62% were male. The common mechanisms of injury included motor vehicle collision (35.8%), followed by falls (21.5%) and inflicted TBI (19%); six children (14.2%) died during their intensive care unit course. The mean CSF mtDNA concentration was 1.10E+05 ± 2.07E+05 and 1.63E+03 ± 1.80E+03 copies/?L in the pediatric TBI and control populations, respectively. Furthermore, the mean CSF mtDNA concentration in pediatric patients who later died or had severe disability was significantly higher than that of the survivors (1.63E+05 ± 2.77E+05 vs. 5.05E+04 ± 6.21E+04 copies/?L) (P < 0.0001). We found a significant correlation between CSF mtDNA and high mobility group box 1, another prototypical DAMP, concentrations (? = 0.574, P < 0.05), supporting the notion that both DAMPs are increased in the CSF after TBI. Our data suggest that CSF mtDNA is a novel DAMP in TBI and appears to be a useful biomarker that correlates with neurological outcome after TBI. Further inquiry into the components of mtDNA that modulate the innate immune response will be helpful in understanding the mechanism of local and systemic inflammation after TBI. PMID:24667615
Walko, Thomas D; Bola, R Aaron; Hong, John D; Au, Alicia K; Bell, Michael J; Kochanek, Patrick M; Clark, Robert S B; Aneja, Rajesh K
Infection with cryptococcal meningitis is uncommon in immunocompetent patients. The major virulence factor is the polysaccharide capsule, while nonencapsulated mutants are generally considered nonpathogenic. The authors present a case of hydrocephalus caused by meningitis from an indolent, nonencapsulated Cryptococcus sp. requiring placement and multiple revisions of a ventriculoperitoneal shunt (VPS). The patient presented with progressively worsening occipital headaches. Computed tomography and magnetic resonance imaging showed significant hydrocephalus with no apparent cause. Her symptoms initially resolved after placement of a VPS, but returned four months later. Cultures of the shunt tubing and cerebrospinalfluid (CSF) showed no bacterial infection. When the symptoms failed to resolve, CSF fungal culture revealed Cryptococcus-like yeast, although the organisms were nonencapsulated, and the cryptococcal antigen was negative. After antibiotic therapy, the symptoms resolved. The unusual clinical presentation delayed the diagnosis, highlighting the importance of understanding the detection, diagnosis, and treatment of meningeal infections caused by C. neoformans.
In the early stages of brain development, cells within the ependymal lining of the neural tube are thought to secrete cerebrospinalfluid (CSF), the so-called neural tube fluid (NTF), whereas before fusion of the neural folds, the neuroepithelium that lines the inside of the neural tube is in contact with amniotic fluid. As the neural tube closes, a membrane formed from these cells invaginates to form the specialized choroid plexus. The choroid plexus is a highly vascularized epithelial cell structure that secretes proteins, including growth factors, into the CSF. Embryonic CSF (e-CSF) contains high concentrations of proteins compared to adult CSF. CSF has been reported to contain nerve growth factor (NGF) and other neurotrophic factors. In this study, total protein concentration and NGF level in e-CSF samples from chick embryos were measured using a dye-based protein assay, enzyme-linked immunosorbent assay (ELISA) and Western blot. The total protein concentration and NGF levels in the CSF decreased from days E10 to E16. There was a rapid increase in total protein content on days E17 and E18, and thereafter the levels decreased from day E19 to day E21. Days E17 and E18 coincide with the onset of neuron migration, proliferation and organization of the cytoarchitecture of the developing cerebral cortex. After that time the total protein concentration and NGF levels decrease until hatching. Since CSF is in contact with the cerebral cortical germinal epithelium, changes in the protein concentration in the CSF could affect neuroepithelial cell proliferation, survival and migration. It is concluded that NGF is not only a constant component of CSF during chick embryogenesis but it might also be involved in cerebral cortical development. PMID:19581095
We describe a boy with Fisher syndrome. He presented the typical symptoms of Fisher syndrome, including external ophthalmoplegia, abnormality of convergence, and areflexia, after an episode of Campylobacter enterocolitis. Atypically, however, anti-GA1 antibody was detected in his serum, though anti-GQ1b and anti-GT1a antibodies were not. In addition, the tau protein level in his cerebrospinalfluid was elevated. Generally, Fisher syndrome is a self-limiting disease and has a good prognosis. In our patient, however, mild diplopia and areflexia persisted 6 months after their onset. Here, we report on the first Fisher syndrome patient with anti-GA1 antibody in the serum and elevated tau protein in the cerebrospinalfluid. PMID:21742448
The characteristics of two nondiffusible indicators, 125I labeled albumin (RISA-125) and blue dextran, were compared by using them simultaneously to measure rate of formation of cerebrospinalfluid (Vf) in in vitro experiments and in a series of ventricul...
A. N. Martins A. Ramirez A. I. Kobrine T. F. Doyle
To study biochemical changes in cerebrospinalfluid (CSF), we developed a reliable technique for repeated collection of CSF in anesthetized strain 13 guinea pigs. The animal's head was mounted in a stereotaxic instrument with ventral tilt at 30, and ciste...
Cerebrospinalfluid (CSF) levels of 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid, homovanillic acid, tryptophan, and ?-aminobutyric acid were measured using high-performance liquid chromatography in 102 infants during the 1st year of life (preterm and term neonates included). CSF levels are expressed versus corrected age (postnatal days – preterm days) which reflects the stage of maturity of the central nervous system. These results are
C. Cann-Moisan; E. Girin; J. D. Giroux; P. Le Bras; J. Caroff
Memantine is a uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist with therapeutic potential in dementia, spasticity and Parkinson's disease. The Ki-value of memantine at the phencyclidine (PCP) binding site of the NMDA receptor is 0.5 ?M in human frontal cortex. We investigated whether concentrations of mementine in cerebrospinalfluid (CSF) and serum samples under therapeutic conditions are in the range of its
The soluble form of Alzheimer's amyloid ? protein (sA?) is associated with high density lipoproteins (HDL) in normal human plasma (BBRC,1994,205,1164–1171). Since sA? is also present in cerebrospinalfluid (CSF) and the lipoprotein pattern of CSF is different from that of plasma, it was of interest to ascertain whether the interaction of sA? with HDL also occurs in CSF. Normal
Alexei R. Koudinov; Natalia V. Koudinova; Asok Kumar; Ronald C. Beavis; Jorge Ghiso
The amyloid beta-protein is deposited in senile plaques and the cerebrovasculature in Alzheimer disease (AD). Since it is derived from proteolytic processing of its parent protein, the amyloid beta-protein precursor (APP), we investigated whether levels of the secreted forms of APP are altered in cerebrospinalfluid (CSF) of AD patients. Quantitative immunoblotting studies with the anti-APP monoclonal antibody P2-1 revealed
William E. van Nostrand; Steven L. Wagner; W. Rodman Shankle; Jeffrey S. Farrow; Malcolm Dick; Johanna M. Rozemuller; Michael A. Kuiper; Erik C. Wolters; James Zimmerman; Carl W. Cotman; Dennis D. Cunningham
Background: The antioxidant status of the tissue affected by ischemia-reperfusion is of great importance for the primary endogenous defense against the free-radical-induced injury. Objective: In this study, we aimed to evaluate the relationship between the activities of antioxidant enzymes [superoxide dismutase (SOD)[, ]glutathione peroxidase (GPX)[, ]and catalase (CAT)] in cerebrospinalfluid (CSF) and severity of hypoxic-ischemic encephalopathy (HIE) in newborns.
Objective: To study the relationship between the activity changes of angiotensin II (Ang II) in plasma, cerebrospinalfluid (CSF) and\\u000a the pathophysiology of vascular dementia (VD) on the one hand and the therapeutic effects of ligustrazine (LIG) on VD and\\u000a its mechanisms on the other hand.Methods: Case grouping: VD group with 50 cases (26 VD patients treated with LIG and
Li Qiang; Wang Jing-zhou; Zhang Li-li; Gao Chang; Zhou Hong-jie; Gao Dong
In this report, we present the results of a multicenter study to test analytic and diagnostic performance of soluble forms of amyloid precursor proteins ? and ? (sAPP? and sAPP?) in the cerebrospinalfluid (CSF) of patients with different forms of dementing conditions. CSF samples were collected from 188 patients with early dementia (mini-mental state examination?20 in majority of cases)
P Lewczuk; H Kamrowski-Kruck; O Peters; I Heuser; F Jessen; J Popp; K Bürger; H Hampel; L Frölich; S Wolf; B Prinz; H Jahn; Ch Luckhaus; R Perneczky; M Hüll; J Schröder; H Kessler; J Pantel; H-J Gertz; H-W Klafki; H Kölsch; U Reulbach; H Esselmann; J M Maler; M Bibl; J Kornhuber; J Wiltfang
The intra vitam diagnosis of dementia with Lewy bodies (DLB) is still based on clinical grounds. So far no technical investigations have been available to support this diagnosis. As for tau protein and ?-amyloid(1–42) (A?42), promising results for the diagnosis of Alzheimer’s disease (AD) have been reported; we evaluated these markers and S-100B protein in cerebrospinalfluid (CSF), using a
Brit Mollenhauer; Lukas Cepek; Mirko Bibl; Jens Wiltfang; Walter J. Schulz-Schaeffer; Barbara Ciesielczyk; Manuela Neumann; Petra Steinacker; Hans A. Kretzschmar; Sigrid Poser; Claudia Trenkwalder; Markus Otto
The levels of prealbumin (PAB, transthyretin) were determined and evaluated in the cerebrospinalfluid (CSF) and serum in\\u000a various subgroups of the multiple sclerosis (MS) patients. In severely disabled patients, serum PAB was elevated more frequently.\\u000a CSF and serum PAB concentrations were higher in treated than in nontreated patients; the values above the upper reference\\u000a limits were also more frequently
M. Hybe?ová; J. Svato?ová; O. Sobek; P. Adam; D. Doležil; D. Adam
The Pyrogallol Red Molybdate (PRM) and Coomassie Brilliant Blue (CBB) protein dye-binding assays have been applied to samples of cerebrospinalfluid (CSF) to investigate protein concentration by dye precipitation prior to sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The protein concentration values of the CSF samples (N=62) showed good agreement between the PRM and CBB assays as indicated by linear regression
There is emerging evidence that lipids play an important role in many neurodegenerative processes, for example in Alzheimer’s\\u000a disease (AD). Although different lipid alterations in the AD brain have been reported, there have only been very few investigations\\u000a of lipid changes in the cerebrospinalfluid (CSF). Recent developments in mass spectrometry (MS) have enabled fast and sensitive\\u000a detection of lipid
M. Kosicek; S. Kirsch; R. Bene; Z. Trkanjec; M. Titlic; L. Bindila; J. Peter-Katalinic; S. Hecimovic
A sensitive bio-analytical assay for amprenavir, a human immunodeficiency virus protease inhibitor, based on reversed-phase liquid chromatography and fluorescence detection, is reported. The analyte is extracted from the matrix, plasma, cerebrospinalfluid (CSF) or semen, with chloroform using propyl-p-hydroxybenzoate as an internal standard. After centrifugation, evaporation of the organic phase and reconstitution in the eluent, the sample is injected into
Rolf W Sparidans; Richard M. W Hoetelmans; Jos H Beijnen
A sensitive and selective ultra-performance liquid chromatographic–tandem mass spectrometric method has been developed for\\u000a analysis of baicalin in the cerebrospinalfluid of rabbits. Samples were separated on a C18 column with a gradient prepared from acetonitrile and 0.3% aqueous formic acid solution as mobile phase. The target compounds\\u000a were quantified by multiple reaction monitoring (MRM) using electrospray ionization (ESI). Intra-and
There are two theories regarding the origin of the lumbar cerebrospinalfluid pulse wave (L-CSFPW): that it arises from the arteries supplying the spinal cord, and that it is due to the pulsations of the brain transmitted through the subarachnoid space of the spine.We investigated L-CSFPW of 11 myelopathic patients with a complete (five patients, CB-group) or an incomplete spinal
Background\\/Aims: We determined cerebrospinalfluid (CSF) concentrations of amyloid-? (A?)1–38, A?1–40, A?1–42, total tau and phospho-tau (p-tau) in order to study their differential expression in frontotemporal dementia (FTD, n = 25) and primary progressive aphasia (PPA, n = 12) as compared to Alzheimer’s dementia (AD, n = 25) and nondemented controls (n = 20). Methods: Commercially available ELISA and electrochemiluminescence
Mirko Bibl; Brit Mollenhauer; Piotr Lewczuk; Hermann Esselmann; Stefanie Wolf; Markus Otto; Johannes Kornhuber; Eckart Rüther; Jens Wiltfang
A simple, sensitive, selective and reproducible method based on anion-exchange liquid chromatography with post-column derivatisation was developed for the determination of eflornithine (2-difluoromethyl-dl-ornithine; DFMO) in human plasma and cerebrospinalfluid. The 1-alkylthio-2-alkyl-isoindoles fluorescent derivative of the drug was separated from the internal standard (MDL 77246A) on an anion-exchange column (PRP-X300, 250×2.1 mm, 7-?m particle size: Hamilton, USA), with retention times
W Hanpitakpong; B Kamanikom; V Banmairuroi; K Na-Bangchang
Advances in molecular biology and immunology provide new, highly sensitive and specific techniques that can be applied to\\u000a analysis of cerebrospinalfluid to enhance the diagnosis and treatment of central nervous system (CNS) infections. In addition\\u000a to improved accuracy and speed of diagnosis, these modalities may offer improved means of monitoring treatment efficacy, establishing\\u000a prognosis, detecting organism resistance, and tracking
BACKGROUND: Avidity determination of antigen-specific immunoglobulin G (IgG) antibodies is an established serological method to differentiate acute from past infections. In order to compare the avidity of varicella-zoster virus (VZV) IgG in pairs of serum and cerebrospinalfluid (CSF) samples, we developed a new technique of avidity testing, the results of which are not influenced by the concentration of specific
Ralf-Herbert Kneitz; Jörg Schubert; Franz Tollmann; Wolfgang Zens; Klaus Hedman; Benedikt Weissbrich
This study reports an improved approach for the determination of neuropeptide levels in human cerebrospinalfluid (CSF). The method is based on sample acidification followed by liquid–liquid extraction (LLE) combined with radioimmunoassay. It was applied to study the recovery and level of some opioid peptides (Met-enkephalin-Arg6-Phe7 and Leu-enkephalin-Arg6), substance P and the substance P1–7 fragment, which are all compounds known
Zhurong Liu; Magnus Welin; Björn Bragee; Fred Nyberg
Background: The clinical diagnosis of Alzheimer’s disease in early stages may be substantiated by the quantification of the biomarkers Abeta42, Abeta40 and total-Tau (t-Tau) in cerebrospinalfluid (CSF). Different commercially available immunosorbent assays yield reliable results, yet the absolute values obtained may differ in between tests. Methods: We used CSF samples from patients that reported to our memory clinic. Enzyme-linked
C. G. Schipke; S. Prokop; F. L. Heppner; I. Heuser; O. Peters
Background\\/Aims\\/Methods: This is a follow-up study from a recent randomized controlled trial conducted at the Women and Children’s Hospital of Buffalo that investigated the use of antimicrobial sutures (AMS) for wound closure during cerebrospinalfluid shunting procedures. Our purpose was to determine the average cost of shunt infections at our institution and estimate the healthcare savings associated with reduced infection
Jonathan Stone; Thomas J. Gruber; Curtis J. Rozzelle